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Publication : The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes.

First Author  Allaire PD Year  2010
Journal  Mol Cell Volume  37
Issue  3 Pages  370-82
PubMed ID  20159556 Mgi Jnum  J:229372
Mgi Id  MGI:5751677 Doi  10.1016/j.molcel.2009.12.037
Citation  Allaire PD, et al. (2010) The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes. Mol Cell 37(3):370-82
abstractText  The DENN domain is an evolutionarily ancient protein module. Mutations in the DENN domain cause developmental defects in plants and human diseases, yet the function of this common module is unknown. We now demonstrate that the connecdenn/DENND1A DENN domain functions as a guanine nucleotide exchange factor (GEF) for Rab35 to regulate endosomal membrane trafficking. Loss of Rab35 activity causes an enlargement of early endosomes and inhibits MHC class I recycling. Moreover, it prevents early endosomal recruitment of EHD1, a common component of tubules involved in endosomal cargo recycling. Our data reveal an enzymatic activity for a DENN domain and demonstrate that distinct Rab GTPases can recruit a common protein machinery to various sites within the endosomal network to establish cargo-selective recycling pathways.
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