Rab coupling protein is selectively degraded by calpain in a Ca 2+-dependent manner

16Citations
Citations of this article
17Readers
Mendeley users who have this article in their library.
Get full text

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, RCPΔPEST, we demonstrated that they are necessary for the cleavage of RCP by calpains. When expressed in A431 cells, RCPΔPEST 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. © 2005 Biochemical Society.

Cite

CITATION STYLE

APA

Marie, N., Lindsay, A. J., & McCaffrey, M. W. (2005). Rab coupling protein is selectively degraded by calpain in a Ca 2+-dependent manner. Biochemical Journal, 389(1), 223–231. https://doi.org/10.1042/BJ20042116

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free