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An activating mutation in AGEF-1, a putative Arf GEF, causes yolk extrusion from C. elegans embryos

FitzPatrick, C.; Skorobogata, O.; Fazlollahi, A. M.; Gauthier, K. D.; Rocheleau, C. E.

2026-02-11 cell biology
10.64898/2026.02.10.705107 bioRxiv
Show abstract

C. elegans AGEF-1, an ortholog of human ARFGEF1 and ARFGEF2, functions with ARF-1, ARF-5 and the AP-1 clathrin adaptor to regulate membrane trafficking. Similar phenotypes induced by the agef-1(vh4[E1028K]) allele and agef-1(RNAi) suggested that agef-1(vh4) was a hypomorph. Here we report that agef-1(vh4) results in extrusion of yolk from the embryo. This is suppressed by RNAi of agef-1, arf-1, arf-5 but not AP-1. Based on structure of the yeast AGEF-1 ortholog, Sec7p, the E1028K change is predicted to activate AGEF-1. We propose that Arf GTPase cycling is required to regulate trafficking with AP-1 but not with Arf effectors regulating yolk trafficking.

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