Advertisement

Affinity, Avidity, and Kinetics of Target Sequence Binding to LC8 Dynein Light Chain Isoforms*

Open AccessPublished:October 02, 2010DOI:https://doi.org/10.1074/jbc.M110.165894
      LC8 dynein light chain (DYNLL) is a highly conserved eukaryotic hub protein with dozens of binding partners and various functions beyond being a subunit of dynein and myosin Va motor proteins. Here, we compared the kinetic and thermodynamic parameters of binding of both mammalian isoforms, DYNLL1 and DYNLL2, to two putative consensus binding motifs (KXTQTX and XG(I/V)QVD) and report only subtle differences. Peptides containing either of the above motifs bind to DYNLL2 with micromolar affinity, whereas a myosin Va peptide (lacking the conserved Gln) and the noncanonical Pak1 peptide bind with Kd values of 9 and 40 μm, respectively. Binding of the KXTQTX motif is enthalpy-driven, although that of all other peptides is both enthalpy- and entropy-driven. Moreover, the KXTQTX motif shows strikingly slower off-rate constant than the other motifs. As most DYNLL partners are homodimeric, we also assessed the binding of bivalent ligands to DYNLL2. Compared with monovalent ligands, a significant avidity effect was found as follows: Kd values of 37 and 3.5 nm for a dimeric myosin Va fragment and a Leu zipper dimerized KXTQTX motif, respectively. Ligand binding kinetics of DYNLL can best be described by a conformational selection model consisting of a slow isomerization and a rapid binding step. We also studied the binding of the phosphomimetic S88E mutant of DYNLL2 to the dimeric myosin Va fragment, and we found a significantly lower apparent Kd value (3 μm). We conclude that the thermodynamic and kinetic fine-tuning of binding of various ligands to DYNLL could have physiological relevance in its interaction network.

      Introduction

      LC8 dynein light chain (DYNLL)
      The abbreviations used are: DYNLL
      LC8 dynein light chain
      CS
      conformational selection
      DIC
      dynein intermediate chain
      IF
      induced fit
      ITC
      isothermal titration calorimetry
      myoVa
      myosin Va
      SPR
      surface plasmon resonance
      nNOS
      nitric-oxide synthase
      Bmf
      Bcl-2-modifying factor
      Bim
      Bcl-2 interacting mediator.
      is a highly conserved small eukaryotic protein. It was originally discovered as a light chain of the dynein (
      • King S.M.
      • Patel-King R.S.
      ) and later of myosin Va (myoVa) (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ) motor protein complexes. However, DYNLL has many interaction partners unrelated to motor proteins. Therefore, it has been suggested that DYNLL is a hub protein that plays important roles in the interactome of eukaryotic cells in various cellular events, including apoptosis, molecular, organelle, and nuclear transport, viral infection, cancer development, and transcription regulation (
      • Barbar E.
      ,
      • Hodi Z.
      • Rapali P.
      • Radnai L.
      • Molnar T.
      • Szenes A.
      • Kardos J.
      • Buday L.
      • Stafford W.
      • Nyitray L.
      ). More intensively studied DYNLL-binding proteins include neuronal nitric-oxide synthase (nNOS) (
      • Jaffrey S.R.
      • Snyder S.H.
      ), myoVa (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ), Bcl-2-modifying factor (Bmf) (
      • Puthalakath H.
      • Villunger A.
      • O'Reilly L.A.
      • Beaumont J.G.
      • Coultas L.
      • Cheney R.E.
      • Huang D.C.
      • Strasser A.
      ), Bcl-2 interacting mediator (Bim) (
      • Puthalakath H.
      • Huang D.C.
      • O'Reilly L.A.
      • King S.M.
      • Strasser A.
      ), dynein intermediate chain (DIC) (
      • Makokha M.
      • Hare M.
      • Li M.
      • Hays T.
      • Barbar E.
      ), the Drosophila swallow mRNA localizing protein (
      • Schnorrer F.
      • Bohmann K.
      • Nüsslein-Volhard C.
      ), and p21-activated protein kinase 1 (Pak1) (
      • Vadlamudi R.K.
      • Bagheri-Yarmand R.
      • Yang Z.
      • Balasenthil S.
      • Nguyen D.
      • Sahin A.A.
      • den Hollander P.
      • Kumar R.
      ,
      • Lu J.
      • Sun Q.
      • Chen X.
      • Wang H.
      • Hu Y.
      • Gu J.
      ). Several solution and crystal structures of apo-DYNLL and complexes with binding peptides have been determined (
      • Tochio H.
      • Ohki S.
      • Zhang Q.
      • Li M.
      • Zhang M.
      ,
      • Liang J.
      • Jaffrey S.R.
      • Guo W.
      • Snyder S.H.
      • Clardy J.
      ,
      • Fan J.
      • Zhang Q.
      • Tochio H.
      • Li M.
      • Zhang M.
      ,
      • Williams J.C.
      • Roulhac P.L.
      • Roy A.G.
      • Vallee R.B.
      • Fitzgerald M.C.
      • Hendrickson W.A.
      ,
      • Benison G.
      • Karplus P.A.
      • Barbar E.
      ,
      • Benison G.
      • Karplus P.A.
      • Barbar E.
      ,
      • Wang W.
      • Lo K.W.
      • Kan H.M.
      • Fan J.S.
      • Zhang M.
      ,
      • Day C.L.
      • Puthalakath H.
      • Skea G.
      • Strasser A.
      • Barsukov I.
      • Lian L.Y.
      • Huang D.C.
      • Hinds M.G.
      ,
      • Makokha M.
      • Huang Y.J.
      • Montelione G.
      • Edison A.S.
      • Barbar E.
      ). DYNLL has a homodimeric structure, and the bound partner peptides lie in two identical grooves formed at the dimerization interface (
      • Tochio H.
      • Ohki S.
      • Zhang Q.
      • Li M.
      • Zhang M.
      ,
      • Liang J.
      • Jaffrey S.R.
      • Guo W.
      • Snyder S.H.
      • Clardy J.
      ,
      • Fan J.
      • Zhang Q.
      • Tochio H.
      • Li M.
      • Zhang M.
      ,
      • Williams J.C.
      • Roulhac P.L.
      • Roy A.G.
      • Vallee R.B.
      • Fitzgerald M.C.
      • Hendrickson W.A.
      ,
      • Benison G.
      • Karplus P.A.
      • Barbar E.
      ,
      • Benison G.
      • Karplus P.A.
      • Barbar E.
      ,
      • Wang W.
      • Lo K.W.
      • Kan H.M.
      • Fan J.S.
      • Zhang M.
      ,
      • Day C.L.
      • Puthalakath H.
      • Skea G.
      • Strasser A.
      • Barsukov I.
      • Lian L.Y.
      • Huang D.C.
      • Hinds M.G.
      ,
      • Makokha M.
      • Huang Y.J.
      • Montelione G.
      • Edison A.S.
      • Barbar E.
      ). Formerly, it was widely assumed that DYNLL could function as a cargo adapter on dynein and myoVa motors (
      • Puthalakath H.
      • Villunger A.
      • O'Reilly L.A.
      • Beaumont J.G.
      • Coultas L.
      • Cheney R.E.
      • Huang D.C.
      • Strasser A.
      ,
      • Naisbitt S.
      • Valtschanoff J.
      • Allison D.W.
      • Sala C.
      • Kim E.
      • Craig A.M.
      • Weinberg R.J.
      • Sheng M.
      ,
      • Pfister K.K.
      • Fisher E.M.
      • Gibbons I.R.
      • Hays T.S.
      • Holzbaur E.L.
      • McIntosh J.R.
      • Porter M.E.
      • Schroer T.A.
      • Vaughan K.T.
      • Witman G.B.
      • King S.M.
      • Vallee R.B.
      ). However, this hypothesis is difficult to reconcile with the symmetric homodimeric structure of DYNLL and most of its partners, including myoVa and DIC. Instead, it has been suggested, based on the effect of DYNLL on its partner proteins, that one of the major roles of DYNLL dimers could be the ability to promote dimerization and stabilization of their interaction partners (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ,
      • Barbar E.
      ,
      • Wang L.
      • Hare M.
      • Hays T.S.
      • Barbar E.
      ).
      DYNLL has two mammalian isoforms (DYNLL1 and DYNLL2; previously known as DLC1 and DLC2 or LC8a and LC8b) (
      • Naisbitt S.
      • Valtschanoff J.
      • Allison D.W.
      • Sala C.
      • Kim E.
      • Craig A.M.
      • Weinberg R.J.
      • Sheng M.
      ,
      • Pfister K.K.
      • Fisher E.M.
      • Gibbons I.R.
      • Hays T.S.
      • Holzbaur E.L.
      • McIntosh J.R.
      • Porter M.E.
      • Schroer T.A.
      • Vaughan K.T.
      • Witman G.B.
      • King S.M.
      • Vallee R.B.
      ) that differ from each other only in six residues. All of these residues are located outside of the ligand binding grooves. Despite their similarity, DYNLL1 and DYNLL2 seem to discriminate binding partners in the cell (
      • Puthalakath H.
      • Villunger A.
      • O'Reilly L.A.
      • Beaumont J.G.
      • Coultas L.
      • Cheney R.E.
      • Huang D.C.
      • Strasser A.
      ,
      • Day C.L.
      • Puthalakath H.
      • Skea G.
      • Strasser A.
      • Barsukov I.
      • Lian L.Y.
      • Huang D.C.
      • Hinds M.G.
      ), although some in vitro studies do not support this finding (
      • Naisbitt S.
      • Valtschanoff J.
      • Allison D.W.
      • Sala C.
      • Kim E.
      • Craig A.M.
      • Weinberg R.J.
      • Sheng M.
      ,
      • Lo K.W.
      • Kogoy J.M.
      • Rasoul B.A.
      • King S.M.
      • Pfister K.K.
      ). The binding grooves are able to interact with short linear sequences, all of which are part of intrinsically disordered regions of the partner proteins. These binding motifs were divided into the following three classes based on sequence similarities: KXTQTX (e.g. Bmf), XG(I/V)QVD (e.g. nNOS), and noncanonical (e.g. myoVa and Pak1) (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ,
      • Fan J.
      • Zhang Q.
      • Tochio H.
      • Li M.
      • Zhang M.
      ,
      • Rodríguez-Crespo I.
      • Yélamos B.
      • Roncal F.
      • Albar J.P.
      • Ortiz de Montellano P.R.
      • Gavilanes F.
      ,
      • Lightcap C.M.
      • Sun S.
      • Lear J.D.
      • Rodeck U.
      • Polenova T.
      • Williams J.C.
      ,
      • Lo K.W.
      • Naisbitt S.
      • Fan J.S.
      • Sheng M.
      • Zhang M.
      ). However, the functional relevance of this classification has never been investigated. A broad range of affinities of various binding peptides and protein fragments (Kd values between 100 nm and 100 μm), determined by different approaches, were reported (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ,
      • Lightcap C.M.
      • Sun S.
      • Lear J.D.
      • Rodeck U.
      • Polenova T.
      • Williams J.C.
      ,
      • Hall J.
      • Hall A.
      • Pursifull N.
      • Barbar E.
      ,
      • Song C.
      • Wen W.
      • Rayala S.K.
      • Chen M.
      • Ma J.
      • Zhang M.
      • Kumar R.
      ,
      • Wagner W.
      • Fodor E.
      • Ginsburg A.
      • Hammer 3rd., J.A.
      ,
      • Nyarko A.
      • Hare M.
      • Hays T.S.
      • Barbar E.
      ). However, it is important to note that many of the partners were shown to exist as homodimers, and therefore DYNLL most likely forms dimer-dimer complexes with its partners (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ,
      • Wang L.
      • Hare M.
      • Hays T.S.
      • Barbar E.
      ). Thus, the observed dissociation constants of monomeric peptides may not be used directly to describe the interaction with dimeric partners, which in fact are bivalent protein ligands (
      • Williams J.C.
      • Roulhac P.L.
      • Roy A.G.
      • Vallee R.B.
      • Fitzgerald M.C.
      • Hendrickson W.A.
      ). Accordingly, we have previously reported an affinity enhancement of dimeric myoVa fragments binding to DYNLL2, compared with a monomeric peptide (
      • Hódi Z.
      • Németh A.L.
      • Radnai L.
      • Hetényi C.
      • Schlett K.
      • Bodor A.
      • Perczel A.
      • Nyitray L.
      ), and the same was noted for a dimeric DIC fragment (
      • Lightcap C.M.
      • Sun S.
      • Lear J.D.
      • Rodeck U.
      • Polenova T.
      • Williams J.C.
      ). However, the quantitative relationship between the affinity and the monomer-dimer state of the binding partner was not investigated in previous studies.
      Regulation of the interactions of DYNLL as a hub protein is not well understood. Binding of the partners to DYNLL could be regulated by phosphorylation of Thr or Ser residues within the DYNLL-binding motif (
      • Lei K.
      • Davis R.J.
      ). Phosphorylation of Ser-88 of DYNLL could be another way of regulation by shifting the monomer-dimer equilibrium strongly to the monomer state, thus eliminating the binding grooves (
      • Song C.
      • Wen W.
      • Rayala S.K.
      • Chen M.
      • Ma J.
      • Zhang M.
      • Kumar R.
      ,
      • Song Y.
      • Benison G.
      • Nyarko A.
      • Hays T.S.
      • Barbar E.
      ). It is not clear which kinase is involved in this regulation; Pak1 was originally shown to phosphorylate DYNLL (
      • Vadlamudi R.K.
      • Bagheri-Yarmand R.
      • Yang Z.
      • Balasenthil S.
      • Nguyen D.
      • Sahin A.A.
      • den Hollander P.
      • Kumar R.
      ,
      • Yang Z.
      • Vadlamudi R.K.
      • Kumar R.
      ); however, a recent study did not support its direct regulatory role (
      • Lightcap C.M.
      • Sun S.
      • Lear J.D.
      • Rodeck U.
      • Polenova T.
      • Williams J.C.
      ).
      Here, we report the kinetic and thermodynamic parameters of binding of DYNLL isoforms to various partners with monovalent and bivalent motifs. We found that the affinity is dramatically increased by the bivalent nature of the binding partners. We also found that the binding reaction of both monovalent and bivalent ligands can be best explained by a conformational selection model. Furthermore, we show that ligands can bind to the S88E phosphomimetic form of DYNLL by pulling the monomer-dimer equilibrium back to the dimer state.

      Acknowledgments

      We give special thanks to Ferenc Tölgyesi for helping in ITC measurements, to Katalin Kékesi for MS analysis, and to András Patthy for peptide synthesis.

      REFERENCES

        • King S.M.
        • Patel-King R.S.
        J. Biol. Chem. 1995; 270: 11445-11452
        • Hódi Z.
        • Németh A.L.
        • Radnai L.
        • Hetényi C.
        • Schlett K.
        • Bodor A.
        • Perczel A.
        • Nyitray L.
        Biochemistry. 2006; 45: 12582-12595
        • Barbar E.
        Biochemistry. 2008; 47: 503-508
        • Hodi Z.
        • Rapali P.
        • Radnai L.
        • Molnar T.
        • Szenes A.
        • Kardos J.
        • Buday L.
        • Stafford W.
        • Nyitray L.
        FEBS J. 2007; 274 (106): 106
        • Jaffrey S.R.
        • Snyder S.H.
        Science. 1996; 274: 774-777
        • Puthalakath H.
        • Villunger A.
        • O'Reilly L.A.
        • Beaumont J.G.
        • Coultas L.
        • Cheney R.E.
        • Huang D.C.
        • Strasser A.
        Science. 2001; 293: 1829-1832
        • Puthalakath H.
        • Huang D.C.
        • O'Reilly L.A.
        • King S.M.
        • Strasser A.
        Mol. Cell. 1999; 3: 287-296
        • Makokha M.
        • Hare M.
        • Li M.
        • Hays T.
        • Barbar E.
        Biochemistry. 2002; 41: 4302-4311
        • Schnorrer F.
        • Bohmann K.
        • Nüsslein-Volhard C.
        Nat. Cell Biol. 2000; 2: 185-190
        • Vadlamudi R.K.
        • Bagheri-Yarmand R.
        • Yang Z.
        • Balasenthil S.
        • Nguyen D.
        • Sahin A.A.
        • den Hollander P.
        • Kumar R.
        Cancer Cell. 2004; 5: 575-585
        • Lu J.
        • Sun Q.
        • Chen X.
        • Wang H.
        • Hu Y.
        • Gu J.
        Biochem. Biophys. Res. Commun. 2005; 331: 153-158
        • Tochio H.
        • Ohki S.
        • Zhang Q.
        • Li M.
        • Zhang M.
        Nat. Struct. Biol. 1998; 5: 965-969
        • Liang J.
        • Jaffrey S.R.
        • Guo W.
        • Snyder S.H.
        • Clardy J.
        Nat. Struct. Biol. 1999; 6: 735-740
        • Fan J.
        • Zhang Q.
        • Tochio H.
        • Li M.
        • Zhang M.
        J. Mol. Biol. 2001; 306: 97-108
        • Williams J.C.
        • Roulhac P.L.
        • Roy A.G.
        • Vallee R.B.
        • Fitzgerald M.C.
        • Hendrickson W.A.
        Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 10028-10033
        • Benison G.
        • Karplus P.A.
        • Barbar E.
        J. Mol. Biol. 2007; 371: 457-468
        • Benison G.
        • Karplus P.A.
        • Barbar E.
        J. Mol. Biol. 2008; 384: 954-966
        • Wang W.
        • Lo K.W.
        • Kan H.M.
        • Fan J.S.
        • Zhang M.
        J. Biol. Chem. 2003; 278: 41491-41499
        • Day C.L.
        • Puthalakath H.
        • Skea G.
        • Strasser A.
        • Barsukov I.
        • Lian L.Y.
        • Huang D.C.
        • Hinds M.G.
        Biochem. J. 2004; 377: 597-605
        • Makokha M.
        • Huang Y.J.
        • Montelione G.
        • Edison A.S.
        • Barbar E.
        Protein Sci. 2004; 13: 727-734
        • Naisbitt S.
        • Valtschanoff J.
        • Allison D.W.
        • Sala C.
        • Kim E.
        • Craig A.M.
        • Weinberg R.J.
        • Sheng M.
        J. Neurosci. 2000; 20: 4524-4534
        • Pfister K.K.
        • Fisher E.M.
        • Gibbons I.R.
        • Hays T.S.
        • Holzbaur E.L.
        • McIntosh J.R.
        • Porter M.E.
        • Schroer T.A.
        • Vaughan K.T.
        • Witman G.B.
        • King S.M.
        • Vallee R.B.
        J. Cell Biol. 2005; 171: 411-413
        • Wang L.
        • Hare M.
        • Hays T.S.
        • Barbar E.
        Biochemistry. 2004; 43: 4611-4620
        • Lo K.W.
        • Kogoy J.M.
        • Rasoul B.A.
        • King S.M.
        • Pfister K.K.
        J. Biol. Chem. 2007; 282: 36871-36878
        • Rodríguez-Crespo I.
        • Yélamos B.
        • Roncal F.
        • Albar J.P.
        • Ortiz de Montellano P.R.
        • Gavilanes F.
        FEBS Lett. 2001; 503: 135-141
        • Lightcap C.M.
        • Sun S.
        • Lear J.D.
        • Rodeck U.
        • Polenova T.
        • Williams J.C.
        J. Biol. Chem. 2008; 283: 27314-27324
        • Lo K.W.
        • Naisbitt S.
        • Fan J.S.
        • Sheng M.
        • Zhang M.
        J. Biol. Chem. 2001; 276: 14059-14066
        • Hall J.
        • Hall A.
        • Pursifull N.
        • Barbar E.
        Biochemistry. 2008; 47: 11940-11952
        • Song C.
        • Wen W.
        • Rayala S.K.
        • Chen M.
        • Ma J.
        • Zhang M.
        • Kumar R.
        J. Biol. Chem. 2008; 283: 4004-4013
        • Wagner W.
        • Fodor E.
        • Ginsburg A.
        • Hammer 3rd., J.A.
        Biochemistry. 2006; 45: 11564-11577
        • Nyarko A.
        • Hare M.
        • Hays T.S.
        • Barbar E.
        Biochemistry. 2004; 43: 15595-15603
        • Lei K.
        • Davis R.J.
        Proc. Natl. Acad. Sci. U.S.A. 2003; 100: 2432-2437
        • Song Y.
        • Benison G.
        • Nyarko A.
        • Hays T.S.
        • Barbar E.
        J. Biol. Chem. 2007; 282: 17272-17279
        • Yang Z.
        • Vadlamudi R.K.
        • Kumar R.
        J. Biol. Chem. 2005; 280: 654-659
        • Sarkar G.
        • Sommer S.S.
        BioTechniques. 1990; 8: 404-407
        • Johnson K.A.
        • Simpson Z.B.
        • Blom T.
        Anal. Biochem. 2009; 387: 20-29
        • Johnson K.A.
        • Simpson Z.B.
        • Blom T.
        Anal. Biochem. 2009; 387: 30-41
        • O'Connor L.
        • Strasser A.
        • O'Reilly L.A.
        • Hausmann G.
        • Adams J.M.
        • Cory S.
        • Huang D.C.
        EMBO J. 1998; 17: 384-395
        • Rodríguez-Crespo I.
        • Straub W.
        • Gavilanes F.
        • Ortiz de Montellano P.R.
        Arch. Biochem. Biophys. 1998; 359: 297-304
        • Kramer R.H.
        • Karpen J.W.
        Nature. 1998; 395: 710-713
        • Pabbisetty K.B.
        • Yue X.
        • Li C.
        • Himanen J.P.
        • Zhou R.
        • Nikolov D.B.
        • Hu L.
        Protein Sci. 2007; 16: 355-361
        • Zhou H.X.
        J. Mol. Biol. 2003; 329: 1-8
        • Zhou H.X.
        Biophys. J. 2006; 91: 3170-3181
        • Navarro-Lérida I.
        • Martínez Moreno M.
        • Roncal F.
        • Gavilanes F.
        • Albar J.P.
        • Rodríguez-Crespo I.
        Proteomics. 2004; 4: 339-346
        • Lajoix A.D.
        • Gross R.
        • Aknin C.
        • Dietz S.
        • Granier C.
        • Laune D.
        Mol. Divers. 2004; 8: 281-290
        • Espindola F.S.
        • Suter D.M.
        • Partata L.B.
        • Cao T.
        • Wolenski J.S.
        • Cheney R.E.
        • King S.M.
        • Mooseker M.S.
        Cell Motil. Cytoskeleton. 2000; 47: 269-281
        • Mammen M.
        • Choi S.K.
        • Whitesides G.M.
        Angew. Chem. Int. Ed. Engl. 1998; 37: 2755-2794
        • Benison G.
        • Chiodo M.
        • Karplus P.A.
        • Barbar E.
        Biochemistry. 2009; 48: 11381-11389
        • Yang P.
        • Yang C.
        • Wirschell M.
        • Davis S.
        J. Biol. Chem. 2009; 284: 31412-31421
        • Fan J.S.
        • Zhang Q.
        • Tochio H.
        • Zhang M.
        J. Biomol. NMR. 2002; 23: 103-114
        • Benison G.
        • Barbar E.
        Methods Enzymol. 2009; 455: 237-258
        • Wlodarski T.
        • Zagrovic B.
        Proc. Natl. Acad. Sci. U.S.A. 2009; 106: 19346-19351
        • Ghaemmaghami S.
        • Huh W.K.
        • Bower K.
        • Howson R.W.
        • Belle A.
        • Dephoure N.
        • O'Shea E.K.
        • Weissman J.S.
        Nature. 2003; 425: 737-741
        • Lightcap C.M.
        • Kari G.
        • Arias-Romero L.E.
        • Chernoff J.
        • Rodeck U.
        • Williams J.C.
        PLoS One. 2009; 4: e6025
        • Fejtova A.
        • Davydova D.
        • Bischof F.
        • Lazarevic V.
        • Altrock W.D.
        • Romorini S.
        • Schöne C.
        • Zuschratter W.
        • Kreutz M.R.
        • Garner C.C.
        • Ziv N.E.
        • Gundelfinger E.D.
        J. Cell Biol. 2009; 185: 341-355
        • Alonso C.
        • Miskin J.
        • Hernáez B.
        • Fernandez-Zapatero P.
        • Soto L.
        • Cantó C.
        • Rodríguez-Crespo I.
        • Dixon L.
        • Escribano J.M.
        J. Virol. 2001; 75: 9819-9827
        • Su Y.
        • Qiao W.
        • Guo T.
        • Tan J.
        • Li Z.
        • Chen Y.
        • Li X.
        • Li Y.
        • Zhou J.
        • Chen Q.
        Cell. Microbiol. 2010; 12: 1098-1107
        • Varma D.
        • Dawn A.
        • Ghosh-Roy A.
        • Weil S.J.
        • Ori-McKenney K.M.
        • Zhao Y.
        • Keen J.
        • Vallee R.B.
        • Williams J.C.
        Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 3493-3498
        • Hinds M.G.
        • Smits C.
        • Fredericks-Short R.
        • Risk J.M.
        • Bailey M.
        • Huang D.C.
        • Day C.L.
        Cell Death Differ. 2007; 14: 128-136