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PMID: 15769254 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rab coupling protein is selectively degraded by calpain in a Ca2+-dependent manner.

The Biochemical journal ·Vol. 389 ·No. Pt 1 ·2005-07-01 ·Pages 223-31

Marie N, Lindsay AJ, McCaffrey MW

Abstract

RCP (Rab coupling protein) belongs to the recently identified Rab11-FIPs (Rab11 family of interacting proteins). All the Rab-FIP members have the ability to bind Rab11 tightly via a Rab-binding domain located near their C-termini. RCP belongs to the class I Rab11-FIP subfamily, characterized by the presence of a conserved C2 domain near its N-terminus. The function of this protein in Rab11-dependent membrane trafficking remains to be fully understood. In the present study, we have identified three putative PEST (Pro, Glu, Ser/Thr-rich) sequences in RCP. PEST motifs play a role in targeting a protein for proteolytic degradation. We have demonstrated that RCP undergoes calcium-dependent degradation which can be prevented by specific calpain inhibitors. Using a mutant, lacking the three PEST sequences, RCP(DeltaPEST), we demonstrated that they are necessary for the cleavage of RCP by calpains. When expressed in A431 cells, RCP(DeltaPEST) displays significantly greater localization to the plasma membrane, compared with the wild-type protein. Similarly, treatment with the calpain inhibitor, calpeptin, results in the redistribution of endogenous RCP to the periphery of the cell. We propose that once the Rab11/RCP-regulated cargo has been delivered from the endocytic recycling compartment to the plasma membrane, RCP is inactivated by calpain-mediated proteolysis.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Motifs Amino Acid Sequence Animals Calcium/metabolism,pharmacology Calpain/metabolism Carrier Proteins/chemistry,genetics,metabolism Cell Line, Tumor Cell Membrane/physiology Conserved Sequence Dipeptides/pharmacology Humans Membrane Proteins/chemistry,genetics,metabolism Mice Secretory Vesicles/physiology Sequence Alignment Sequence Homology, Amino Acid
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins Dipeptides Membrane Proteins RAB11FIP1 protein, human calpeptin Calpain Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Marie Nicolas
Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
Lindsay Andrew J
McCaffrey Mary W
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20042116
Published
2005-07-01
Pages
223-31
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1184555
Subset
IM
External Links
PubMed source DOI: 10.1042/BJ20042116 PMC Full Text View journal details
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