The J-domain Protein Rme-8 Interacts with Hsc70 to Control Clathrin-dependent Endocytosis in Drosophila

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2004 Mar 31

PMID 15051737

Citations 42

Authors

Henry C Chang

Michael Hull

Ira Mellman

Affiliations

Soon will be listed here.

Abstract

By screening for mutants exhibiting interactions with a dominant-negative dynamin, we have identified the Drosophila homologue of receptor-mediated endocytosis (Rme) 8, a J-domain-containing protein previously shown to be required for endocytosis in Caenorhabditis elegans. Analysis of Drosophila Rme-8 mutants showed that internalization of Bride of sevenless and the uptake of tracers were blocked. In addition, endosomal organization and the distribution of clathrin were greatly disrupted in Rme-8 cells, suggesting that Rme-8 participates in a clathrin-dependent process. The phenotypes of Rme-8 mutants bear a strong resemblance to those of Hsc70-4, suggesting that these two genes act in a common pathway. Indeed, biochemical and genetic data demonstrated that Rme-8 interacts specifically with Hsc70-4 via its J-domain. Thus, Rme-8 appears to function as an unexpected but critical cochaperone with Hsc70 in endocytosis. Because Hsc70 is known to act in clathrin uncoating along with auxilin, another J-protein, its interaction with Rme-8 indicates that Hsc70 can act with multiple cofactors, possibly explaining its pleiotropic effects on the endocytic pathway.

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References

Gonzalez-Gaitan M, Jackle H . Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell. 1997; 88(6):767-76. DOI: 10.1016/s0092-8674(00)81923-6. View

Poodry C, Edgar L . Reversible alteration in the neuromuscular junctions of Drosophila melanogaster bearing a temperature-sensitive mutation, shibire. J Cell Biol. 1979; 81(3):520-7. PMC: 2110401. DOI: 10.1083/jcb.81.3.520. View

Bukau B, Horwich A . The Hsp70 and Hsp60 chaperone machines. Cell. 1998; 92(3):351-66. DOI: 10.1016/s0092-8674(00)80928-9. View

Chen B, Chu T, Harms E, Gergen J, Strickland S . Mapping of Drosophila mutations using site-specific male recombination. Genetics. 1998; 149(1):157-63. PMC: 1460155. DOI: 10.1093/genetics/149.1.157. View

Hannan L, Newmyer S, Schmid S . ATP- and cytosol-dependent release of adaptor proteins from clathrin-coated vesicles: A dual role for Hsc70. Mol Biol Cell. 1998; 9(8):2217-29. PMC: 25474. DOI: 10.1091/mbc.9.8.2217. View

Sunio A, Metcalf A, Kramer H . Genetic dissection of endocytic trafficking in Drosophila using a horseradish peroxidase-bride of sevenless chimera: hook is required for normal maturation of multivesicular endosomes. Mol Biol Cell. 1999; 10(4):847-59. PMC: 25206. DOI: 10.1091/mbc.10.4.847. View

Kelley W . Molecular chaperones: How J domains turn on Hsp70s. Curr Biol. 1999; 9(8):R305-8. DOI: 10.1016/s0960-9822(99)80185-7. View

Elefant F, Palter K . Tissue-specific expression of dominant negative mutant Drosophila HSC70 causes developmental defects and lethality. Mol Biol Cell. 1999; 10(7):2101-17. PMC: 25422. DOI: 10.1091/mbc.10.7.2101. View

Spradling A, Stern D, Beaton A, Rhem E, Laverty T, Mozden N . The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. Genetics. 1999; 153(1):135-77. PMC: 1460730. DOI: 10.1093/genetics/153.1.135. View

10.

Pishvaee B, Costaguta G, Yeung B, Ryazantsev S, Greener T, Greene L . A yeast DNA J protein required for uncoating of clathrin-coated vesicles in vivo. Nat Cell Biol. 2001; 2(12):958-63. DOI: 10.1038/35046619. View

11.

Newmyer S, Schmid S . Dominant-interfering Hsc70 mutants disrupt multiple stages of the clathrin-coated vesicle cycle in vivo. J Cell Biol. 2001; 152(3):607-20. PMC: 2196005. DOI: 10.1083/jcb.152.3.607. View

12.

Greener T, Grant B, Zhang Y, Wu X, Greene L, Hirsh D . Caenorhabditis elegans auxilin: a J-domain protein essential for clathrin-mediated endocytosis in vivo. Nat Cell Biol. 2001; 3(2):215-9. DOI: 10.1038/35055137. View

13.

Kirchhausen T . Three ways to make a vesicle. Nat Rev Mol Cell Biol. 2001; 1(3):187-98. DOI: 10.1038/35043117. View

14.

Zhang Y, Grant B, Hirsh D . RME-8, a conserved J-domain protein, is required for endocytosis in Caenorhabditis elegans. Mol Biol Cell. 2001; 12(7):2011-21. PMC: 55649. DOI: 10.1091/mbc.12.7.2011. View

15.

Damke H, Binns D, Ueda H, Schmid S, Baba T . Dynamin GTPase domain mutants block endocytic vesicle formation at morphologically distinct stages. Mol Biol Cell. 2001; 12(9):2578-89. PMC: 59696. DOI: 10.1091/mbc.12.9.2578. View

16.

Morgan J, Prasad K, Jin S, Augustine G, Lafer E . Uncoating of clathrin-coated vesicles in presynaptic terminals: roles for Hsc70 and auxilin. Neuron. 2001; 32(2):289-300. DOI: 10.1016/s0896-6273(01)00467-6. View

17.

Lloyd T, Atkinson R, Wu M, Zhou Y, Pennetta G, Bellen H . Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell. 2002; 108(2):261-9. DOI: 10.1016/s0092-8674(02)00611-6. View

18.

Campbell R, Tour O, Palmer A, Steinbach P, Baird G, Zacharias D . A monomeric red fluorescent protein. Proc Natl Acad Sci U S A. 2002; 99(12):7877-82. PMC: 122988. DOI: 10.1073/pnas.082243699. View

19.

Chang H, Newmyer S, Hull M, Ebersold M, Schmid S, Mellman I . Hsc70 is required for endocytosis and clathrin function in Drosophila. J Cell Biol. 2002; 159(3):477-87. PMC: 2173062. DOI: 10.1083/jcb.200205086. View

20.

Tomancak P, Beaton A, Weiszmann R, Kwan E, Shu S, Lewis S . Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol. 2003; 3(12):RESEARCH0088. PMC: 151190. DOI: 10.1186/gb-2002-3-12-research0088. View