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CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl

Cormont, M., Metón, I., Mari, M., Monzo, P., Keslair, F., Gaskin, C., McGraw, T. E. & Le Marchand-Brustel, Y., Feb-2003, In : Traffic. 4, 2, p. 97-112 16 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Mireille Cormont
  • Isidoro Metón
  • Muriel Mari
  • Pascale Monzo
  • Frédérique Keslair
  • Chantell Gaskin
  • Timothy E McGraw
  • Yannick Le Marchand-Brustel

The small GTPase Rab4 is involved in endocytosis through sorting and recycling early endosomes. To better understand the role of Rab4 in regulation of vesicular trafficking, we searched for effectors that specifically interact with Rab4-Q67L, the GTP-bound form of Rab4. We cloned an ubiquitous 80-kDa protein, identical to CD2-associated protein/Cas ligand with multiple SH3 domains (CD2AP/CMS), that interacts with Rab4-Q67L in the yeast two-hybrid system and in vitro. CD2AP/CMS expressed in mammalian cells was localized to punctate structures and along actin filaments. None of the known markers of early endosomes [Early Endosomes Antigen 1 (EEA1), Rab5 and Rab11] colocalized with the CD2AP/CMS-positive vesicles. However, coexpression of Rab4-Q67L with CD2AP/CMS induces a significant enlargement of EEA1-positive early endosomes. Rab4, CD2AP/CMS and Rab7 colocalized in these modified endosomes. Coexpression of c-Cbl and CD2AP/CMS also resulted in an enlargement of early endosomes. Using various truncated forms of CD2AP/CMS, we demonstrate that early endosomes enlargement requires that CD2AP/CMS interacts with both Rab4 and c-Cbl. The expression of a truncated form of CD2AP/CMS that retains the ability to interact with Rab4 but not c-Cbl inhibits ligand-induced PDGF receptor degradation. We propose that CD2AP/CMS, through interactions with Rab4 and c-Cbl, controls early endosome morphology and may play a role in traffic between early and late endosomes, and thus in the degradative pathway.

Original languageEnglish
Pages (from-to)97-112
Number of pages16
JournalTraffic
Volume4
Issue number2
Publication statusPublished - Feb-2003
Externally publishedYes

    Keywords

  • Actin Cytoskeleton, Adaptor Proteins, Signal Transducing, Animals, CHO Cells, Cricetinae, Cytoskeletal Proteins, Endosomes, Humans, Microscopy, Fluorescence, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Receptors, Platelet-Derived Growth Factor, Receptors, Transferrin, Ubiquitin-Protein Ligases, rab4 GTP-Binding Proteins

ID: 16003854