Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory proteins to dynein motors

Juliati Rahajeng, Sai S P Giridharan, Naava Naslavsky, Steven H Caplan

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Endocytosis is a conserved cellular process in which nutrients, lipids, and receptors are internalized and transported to early endosomes, where they are sorted and either channeled to degradative pathways or recycled to the plasma membrane. MICAL-L1 and EHD1 are important regulatory proteins that control key endocytic transport steps. However, the precise mechanisms by which they mediate transport, and particularly the mode by which they connect to motor proteins, have remained enigmatic. Here we have identified the collapsin response mediator protein-2 (Crmp2) as an interaction partner of MICAL-L1 in non-neuronal cells. Crmp2 interacts with tubulin dimers and kinesin and negatively regulates dynein-based transport in neuronal cells, but its expression and function in non-neuronal cells have remained poorly characterized. Upon Crmp2 depletion, we observed dramatic relocalization of internalized transferrin (Tf) from peripheral vesicles to the endocytic recycling compartment (ERC), similar to the effect of depleting either MICAL-L1 or EHD1. Moreover, Tf relocalization to the ERC could be inhibited by interfering with microtubule polymerization, consistent with a role for uncoupled motor protein-based transport upon depletion of Crmp2, MICAL-L1, or EHD1. Finally, transfection of dynamitin, a component of the dynactin complex whose overexpression inhibits dynein activity, prevented the relocalization of internalized Tf to the ERC upon depletion of Crmp2, MICAL-L1, or EHD1. These data provide the first trafficking regulatory role for Crmp2 in non-neuronal cells and support a model in which Crmp2 is an important endocytic regulatory protein that links MICAL-L1·EHD1-based vesicular transport to dynein motors.

Original languageEnglish (US)
Pages (from-to)31918-31922
Number of pages5
JournalJournal of Biological Chemistry
Volume285
Issue number42
DOIs
StatePublished - Oct 15 2010

Fingerprint

Dyneins
Transferrin
Proteins
Recycling
Kinesin
Transport Vesicles
Endosomes
Protein Transport
Cell membranes
Tubulin
Endocytosis
collapsin response mediator protein-2
Microtubules
Polymerization
Dimers
Nutrients
Transfection
Cell Membrane
Lipids
Food

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory proteins to dynein motors. / Rahajeng, Juliati; Giridharan, Sai S P; Naslavsky, Naava; Caplan, Steven H.

In: Journal of Biological Chemistry, Vol. 285, No. 42, 15.10.2010, p. 31918-31922.

Research output: Contribution to journalArticle

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