HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kang, S. Articles by Collawn, J. F. Search for Related Content PubMed PubMed Citation Articles by Kang, S. Articles by Collawn, J. F. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 32, 20644-20652, August 7, 1998

Structural Requirements for Major Histocompatibility Complex Class II Invariant Chain Endocytosis and Lysosomal Targeting

From the Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005

The invariant chain (Ii) targets newly synthesized major histocompatibility complex class II complexes to a lysosome-like compartment. Previously, we demonstrated that both the cytoplasmic tail (CT) and transmembrane (TM) domains of Ii were sufficient for this targeting and that the CT contains two di-leucine signals, ³DQRDLI⁸ and ¹²EQLPML¹⁷ (Odorizzi, C. G., Trowbridge, I. S., Xue, L., Hopkins, C. R., Davis, C. D., and Collawn, J. F. (1994) J. Cell Biol. 126, 317-330). In the present study, we examined the relationship between signals required for endocytosis and those required for lysosomal targeting by analyzing Ii-transferrin receptor chimeras in quantitative transport assays. Analysis of the Ii CT signals indicates that although ³DQRDLI⁸ is necessary and sufficient for endocytosis, either di-leucine signal is sufficient for lysosomal targeting. Deletions between the two signals reduced endocytosis without affecting lysosomal targeting. Transplantation of the DQRDLI sequence in place of the EQLPML signal produced a chimera that trafficked normally, suggesting that this di-leucine sequence coded for an independent structural motif. Structure-function analysis of the Ii TM region showed that when Ii TM residues 11-19 and 20-29 were individually substituted for the corresponding regions in the wild-type transferrin receptor, lysosomal targeting was dramatically enhanced, whereas endocytosis remained unchanged. Our results therefore demonstrate that the structural requirements for Ii endocytosis and lysosomal targeting are different.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Szaszak, H.-D. Chen, H.-C. Chen, A. Baukal, L. Hunyady, and K. J Catt Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein J. Endocrinol., November 1, 2008; 199(2): 165 - 176. [Abstract] [Full Text] [PDF]

				C. Scott, M. E. Higgins, J. P. Davies, and Y. A. Ioannou Targeting of NPC1 to Late Endosomes Involves Multiple Signals, Including One Residing within the Putative Sterol-sensing Domain J. Biol. Chem., November 12, 2004; 279(46): 48214 - 48223. [Abstract] [Full Text] [PDF]

				J. A. Shumilla, V. Lacaille, T. M. C. Hornell, J. Huang, S. Narasimhan, D. A. Relman, and E. D. Mellins Bordetella pertussis Infection of Primary Human Monocytes Alters HLA-DR Expression Infect. Immun., March 1, 2004; 72(3): 1450 - 1462. [Abstract] [Full Text] [PDF]

				D. G. Rodionov, S. Honing, A. Silye, T. L. Kongsvik, K. von Figura, and O. Bakke Structural Requirements for Interactions between Leucine-sorting Signals and Clathrin-associated Adaptor Protein Complex AP3 J. Biol. Chem., November 27, 2002; 277(49): 47436 - 47443. [Abstract] [Full Text] [PDF]

				T. L. Kongsvik, S. Honing, O. Bakke, and D. G. Rodionov Mechanism of Interaction between Leucine-based Sorting Signals from the Invariant Chain and Clathrin-associated Adaptor Protein Complexes AP1 and AP2 J. Biol. Chem., May 3, 2002; 277(19): 16484 - 16488. [Abstract] [Full Text] [PDF]

				J. T. West, S. K. Weldon, S. Wyss, X. Lin, Q. Yu, M. Thali, and E. Hunter Mutation of the Dominant Endocytosis Motif in Human Immunodeficiency Virus Type 1 gp41 Can Complement Matrix Mutations without Increasing Env Incorporation J. Virol., March 7, 2002; 76(7): 3338 - 3349. [Abstract] [Full Text] [PDF]

				J. G. Alb Jr., S. E. Phillips, K. Rostand, X. Cui, J. Pinxteren, L. Cotlin, T. Manning, S. Guo, J. D. York, H. Sontheimer, et al. Genetic Ablation of Phosphatidylinositol Transfer Protein Function in Murine Embryonic Stem Cells Mol. Biol. Cell, March 1, 2002; 13(3): 739 - 754. [Abstract] [Full Text] [PDF]

				L. Zaliauskiene, S. Kang, C. G. Brouillette, J. Lebowitz, R. B. Arani, and J. F. Collawn Down-Regulation of Cell Surface Receptors Is Modulated by Polar Residues within the Transmembrane Domain Mol. Biol. Cell, August 1, 2000; 11(8): 2643 - 2655. [Abstract] [Full Text]

				C. Ochsenbauer, S. R. Dubay, and E. Hunter The Rous Sarcoma Virus Env Glycoprotein Contains a Highly Conserved Motif Homologous to Tyrosine-Based Endocytosis Signals and Displays an Unusual Internalization Phenotype Mol. Cell. Biol., January 1, 2000; 20(1): 249 - 260. [Abstract] [Full Text]

				L. F. Cotlin, M. A. Siddiqui, F. Simpson, and J. F. Collawn Casein Kinase II Activity Is Required for Transferrin Receptor Endocytosis J. Biol. Chem., October 22, 1999; 274(43): 30550 - 30556. [Abstract] [Full Text] [PDF]

				J. B. Ashman and J. Miller A Role for the Transmembrane Domain in the Trimerization of the MHC Class II-Associated Invariant Chain J. Immunol., September 1, 1999; 163(5): 2704 - 2712. [Abstract] [Full Text] [PDF]

				P. A. Calvo, D. W. Frank, B. M. Bieler, J. F. Berson, and M. S. Marks A Cytoplasmic Sequence in Human Tyrosinase Defines a Second Class of Di-leucine-based Sorting Signals for Late Endosomal and Lysosomal Delivery J. Biol. Chem., April 30, 1999; 274(18): 12780 - 12789. [Abstract] [Full Text] [PDF]

				L. S. Prince, K. Peter, S. R. Hatton, L. Zaliauskiene, L. F. Cotlin, J. P. Clancy, R. B. Marchase, and J. F. Collawn Efficient Endocytosis of the Cystic Fibrosis Transmembrane Conductance Regulator Requires a Tyrosine-based Signal J. Biol. Chem., February 5, 1999; 274(6): 3602 - 3609. [Abstract] [Full Text] [PDF]