RRC ID 46434
著者 Sasidharan N, Sumakovic M, Hannemann M, Hegermann J, Liewald JF, Olendrowitz C, Koenig S, Grant BD, Rizzoli SO, Gottschalk A, Eimer S.
タイトル RAB-5 and RAB-10 cooperate to regulate neuropeptide release in Caenorhabditis elegans.
ジャーナル Proc Natl Acad Sci U S A
Abstract Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all Caenorhabditis elegans Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from C. elegans motoneurons. rab-5 and rab-10 mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other's GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi-endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.
巻・号 109(46)
ページ 18944-9
公開日 2012-11-13
DOI 10.1073/pnas.1203306109
PII 1203306109
PMID 23100538
PMC PMC3503202
MeSH Animals Biological Transport / physiology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Endosomes / genetics Endosomes / metabolism Exocytosis / physiology Golgi Apparatus / genetics Golgi Apparatus / metabolism Motor Neurons / metabolism* Mutation Neuropeptides / metabolism* Secretory Vesicles / genetics Secretory Vesicles / metabolism* Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism* rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism*
IF 9.412
引用数 23
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm2241 tm3255 tm2991 tm2081 tm2095 tm2306 tm2058 tm2089 tm2466