Both in vivo and in vitro the distribution of the resident plasma membrane adhesion protein, CD44, is restricted to the basolateral domain of polarized epithelial cells, suggesting a role in interepithelial interactions. To determine how this localization might be regulated, a range of CD44 cytoplasmic domain mutations were generated and a minimal 5 amino acid sequence, His-Leu-Val-Asn-Lys, was identified which when deleted results in expression of CD44 on the apical microvillal membrane. Further mutagenesis throughout this regions pinpointed a critical di-hydrophobic motif, Leu/Val. The ability of wild type but not mutant CD44 cytoplasmic domains to redirect an apically targeted protein, placental alkaline phosphatase, to the basolateral plasma membrane demonstrates that this sequence can function as a dominant localization signal. This His-Lys sequence is spatially separate from other CD44 regulatory elements and as discussed here, a comparison with known basolateral sorting sequences identified in other transmembrane proteins suggests that a distinct mechanism operates to retain resident plasma membrane proteins in their correct plasma membrane subdomains.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J.-L. Lee, M.-J. Wang, and J.-Y. Chen Acetylation and activation of STAT3 mediated by nuclear translocation of CD44 J. Cell Biol., June 15, 2009; 185(6): 949 - 957. [Abstract] [Full Text] [PDF]

				M. Kato, S. Khan, E. d'Aniello, K. J. McDonald, and D. N. J. Hart The Novel Endocytic and Phagocytic C-Type Lectin Receptor DCL-1/CD302 on Macrophages Is Colocalized with F-Actin, Suggesting a Role in Cell Adhesion and Migration J. Immunol., November 1, 2007; 179(9): 6052 - 6063. [Abstract] [Full Text] [PDF]

				H. C. Li, E. Y. Li, L. Neumeier, L. Conforti, and M. Soleimani Identification of a novel signal in the cytoplasmic tail of the Na+:HCO3- cotransporter NBC1 that mediates basolateral targeting Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1245 - F1255. [Abstract] [Full Text] [PDF]

				C. Wild-Bode, K. Fellerer, J. Kugler, C. Haass, and A. Capell A Basolateral Sorting Signal Directs ADAM10 to Adherens Junctions and Is Required for Its Function in Cell Migration J. Biol. Chem., August 18, 2006; 281(33): 23824 - 23829. [Abstract] [Full Text] [PDF]

				M. Tanemoto, T. Abe, and S. Ito PDZ-Binding and Di-Hydrophobic Motifs Regulate Distribution of Kir4.1 Channels in Renal Cells J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2608 - 2614. [Abstract] [Full Text] [PDF]

				H. A. Iverson, D. Fox III, L. S. Nadler, R. E. Klevit, and N. M. Nathanson Identification and Structural Determination of the M3 Muscarinic Acetylcholine Receptor Basolateral Sorting Signal J. Biol. Chem., July 1, 2005; 280(26): 24568 - 24575. [Abstract] [Full Text] [PDF]

				A. A. Deora, D. Gravotta, G. Kreitzer, J. Hu, D. Bok, and E. Rodriguez-Boulan The Basolateral Targeting Signal of CD147 (EMMPRIN) Consists of a Single Leucine and Is Not Recognized by Retinal Pigment Epithelium Mol. Biol. Cell, September 1, 2004; 15(9): 4148 - 4165. [Abstract] [Full Text] [PDF]

				U. Sundberg, N. Beauchemin, and B. Obrink The cytoplasmic domain of CEACAM1-L controls its lateral localization and the organization of desmosomes in polarized epithelial cells J. Cell Sci., March 1, 2004; 117(7): 1091 - 1104. [Abstract] [Full Text] [PDF]

				R. F. Thorne, J. W. Legg, and C. M. Isacke The role of the CD44 transmembrane and cytoplasmic domains in co-ordinating adhesive and signalling events J. Cell Sci., January 22, 2004; 117(3): 373 - 380. [Abstract] [Full Text] [PDF]

				S. A. Rajasekaran, G. Anilkumar, E. Oshima, J. U. Bowie, H. Liu, W. Heston, N. H. Bander, and A. K. Rajasekaran A Novel Cytoplasmic Tail MXXXL Motif Mediates the Internalization of Prostate-specific Membrane Antigen Mol. Biol. Cell, December 1, 2003; 14(12): 4835 - 4845. [Abstract] [Full Text] [PDF]

				M. A. Chellaiah, R. S. Biswas, S. R. Rittling, D. T. Denhardt, and K. A. Hruska Rho-dependent Rho Kinase Activation Increases CD44 Surface Expression and Bone Resorption in Osteoclasts J. Biol. Chem., August 1, 2003; 278(31): 29086 - 29097. [Abstract] [Full Text] [PDF]

				K. Kizhatil and L. M. Albritton System y+ localizes to different membrane subdomains in the basolateral plasma membrane of epithelial cells Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1784 - C1794. [Abstract] [Full Text] [PDF]

				H. Suemizu, M. Radosavljevic, M. Kimura, S. Sadahiro, S. Yoshimura, S. Bahram, and H. Inoko A basolateral sorting motif in the MICA cytoplasmic tail PNAS, February 14, 2002; (2002) 52701099. [Abstract] [Full Text] [PDF]

				V. Bello, J. W. Goding, V. Greengrass, A. Sali, V. Dubljevic, C. Lenoir, G. Trugnan, and M. Maurice Characterization of a Di-leucine-based Signal in the Cytoplasmic Tail of the Nucleotide-pyrophosphatase NPP1 That Mediates Basolateral Targeting but not Endocytosis Mol. Biol. Cell, October 1, 2001; 12(10): 3004 - 3015. [Abstract] [Full Text] [PDF]

				V Gouyer, E Leteurtre, P Delmotte, W. Steelant, M. Krzewinski-Recchi, J. Zanetta, T Lesuffleur, G Trugnan, P Delannoy, and G Huet Differential effect of GalNAc(&agr;)-O-bn on intracellular trafficking in enterocytic HT-29 and Caco-2 cells: correlation with the glycosyltransferase expression pattern J. Cell Sci., January 4, 2001; 114(8): 1455 - 1471. [Abstract] [PDF]

				H Sheikh, H Yarwood, A Ashworth, and C. Isacke Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor J. Cell Sci., January 3, 2000; 113(6): 1021 - 1032. [Abstract] [PDF]

				W. El Nemer, Y. Colin, C. Bauvy, P. Codogno, R. H. Fraser, J. P. Cartron, and C. L. Van Kim Isoforms of the Lutheran/Basal Cell Adhesion Molecule Glycoprotein Are Differentially Delivered in Polarized Epithelial Cells. MAPPING OF THE BASOLATERAL SORTING SIGNAL TO A CYTOPLASMIC DI-LEUCINE MOTIF J. Biol. Chem., November 5, 1999; 274(45): 31903 - 31908. [Abstract] [Full Text] [PDF]

				S. Oliferenko, K. Paiha, T. Harder, V. Gerke, C. Schwarzler, H. Schwarz, H. Beug, U. Gunthert, and L. A. Huber Analysis of CD44-containing Lipid Rafts: Recruitment of Annexin II and Stabilization by the Actin Cytoskeleton J. Cell Biol., August 23, 1999; 146(4): 843 - 854. [Abstract] [Full Text] [PDF]

				A. M. Kachinsky, S. C. Froehner, and S. L. Milgram A PDZ-containing Scaffold Related to the Dystrophin Complex at the Basolateral Membrane of Epithelial Cells J. Cell Biol., April 19, 1999; 145(2): 391 - 402. [Abstract] [Full Text] [PDF]

				T. Simmen, M. Nobile, J. S. Bonifacino, and W. Hunziker Basolateral Sorting of Furin in MDCK Cells Requires a Phenylalanine-Isoleucine Motif Together with an Acidic Amino Acid Cluster Mol. Cell. Biol., April 1, 1999; 19(4): 3136 - 3144. [Abstract] [Full Text] [PDF]

				R. Schülein, R. Hermosilla, A. Oksche, M. Dehe, B. Wiesner, G. Krause, and W. Rosenthal A Dileucine Sequence and an Upstream Glutamate Residue in the Intracellular Carboxyl Terminus of the Vasopressin V2 Receptor Are Essential for Cell Surface Transport in COS.M6 Cells Mol. Pharmacol., September 1, 1998; 54(3): 525 - 535. [Abstract] [Full Text]

				C. Geisler, J. Dietrich, B. L. Nielsen, J. Kastrup, J. P. H. Lauritsen, N. Odum, and M. D. Christensen Leucine-based Receptor Sorting Motifs Are Dependent on the Spacing Relative to the Plasma Membrane J. Biol. Chem., August 14, 1998; 273(33): 21316 - 21323. [Abstract] [Full Text] [PDF]

				I. Beau, M.-T. Groyer-Picard, A. Le Bivic, B. Vannier, H. Loosfelt, E. Milgrom, and M. Misrahi The Basolateral Localization Signal of the Follicle-stimulating Hormone Receptor J. Biol. Chem., July 17, 1998; 273(29): 18610 - 18616. [Abstract] [Full Text] [PDF]

				J. Dietrich, J. Kastrup, B. L. Nielsen, N. Odum, and C. Geisler Regulation and Function of the CD3gamma DxxxLL Motif: A Binding Site for Adaptor Protein-1 and Adaptor Protein-2 in Vitro J. Cell Biol., July 28, 1997; 138(2): 271 - 281. [Abstract] [Full Text] [PDF]

				G. Odorizzi and I. S. Trowbridge Structural Requirements for Major Histocompatibility Complex Class II Invariant Chain Trafficking in Polarized Madin-Darby Canine Kidney Cells J. Biol. Chem., May 2, 1997; 272(18): 11757 - 11762. [Abstract] [Full Text] [PDF]

				I. V. Sandoval, S. Martinez-Arca, J. Valdueza, S. Palacios, and G. D. Holman Distinct Reading of Different Structural Determinants Modulates the Dileucine-mediated Transport Steps of the Lysosomal Membrane Protein LIMPII and the Insulin-sensitive Glucose Transporter GLUT4 J. Biol. Chem., December 15, 2000; 275(51): 39874 - 39885. [Abstract] [Full Text] [PDF]

				A.-Q. Sun, M. A. Arrese, L. Zeng, I'K. Swaby, M.-M. Zhou, and F. J. Suchy The Rat Liver Na+/Bile Acid Cotransporter. IMPORTANCE OF THE CYTOPLASMIC TAIL TO FUNCTION AND PLASMA MEMBRANE TARGETING J. Biol. Chem., February 23, 2001; 276(9): 6825 - 6833. [Abstract] [Full Text] [PDF]

				K. C. Miranda, T. Khromykh, P. Christy, T. L. Le, C. J. Gottardi, A. S. Yap, J. L. Stow, and R. D. Teasdale A Dileucine Motif Targets E-cadherin to the Basolateral Cell Surface in Madin-Darby Canine Kidney and LLC-PK1 Epithelial Cells J. Biol. Chem., June 15, 2001; 276(25): 22565 - 22572. [Abstract] [Full Text] [PDF]

				H. Suemizu, M. Radosavljevic, M. Kimura, S. Sadahiro, S. Yoshimura, S. Bahram, and H. Inoko A basolateral sorting motif in the MICA cytoplasmic tail PNAS, March 5, 2002; 99(5): 2971 - 2976. [Abstract] [Full Text] [PDF]