Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors

Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors

A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activat...

Function of Rab3 GDP–GTP Exchange

Three lines of evidence suggest that rabphilin and rab3 dissociation occur in conjunction with Ca-triggered A felicitous convergence of independent lines of resynaptic vesicle fusion, and that they occur after docksearch, biochemistry in mammals and genetics in C. ing but before endocytosis of vesicles: 1. Tetanus and elegans, has given us unexpected insight into the biolbotulinum toxins inhibi...

Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.

Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-Å resolution the first structure of a...

characterization of stimulatory GDP / GTP p 21 - like small GTP - binding proteins ) and GDP / GTP exchange protein for smg p 21 s ( ras

Evolution of the Rab family of small GTP-binding proteins.

Rab proteins are small GTP-binding proteins that form the largest family within the Ras superfamily. Rab proteins regulate vesicular trafficking pathways, behaving as membrane-associated molecular switches. Here, we have identified the complete Rab families in the Caenorhabditis elegans (29 members), Drosophila melanogaster (29), Homo sapiens (60) and Arabidopsis thaliana (57), and we defined c...