MPK-1 ERK controls membrane organization in C. elegans oogenesis via a sex-determination module

Swathi Arur, Mitsue Ohmachi, Matt Berkseth, Sudhir Nayak, David Hansen, David A Zarkower, Tim Schedl

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46 Scopus citations


Tissues that generate specialized cell types in a production line must coordinate developmental mechanisms with physiological demand, although how this occurs is largely unknown. In the Caenorhabditis elegans hermaphrodite, the developmental sex-determination cascade specifies gamete sex in the distal germline, while physiological sperm signaling activates MPK-1/ERK in the proximal germline to control plasma membrane biogenesis and organization during oogenesis. We discovered repeated utilization of a self-contained negative regulatory module, consisting of NOS-3 translational repressor, FEM-CUL-2 (E3 ubiquitin ligase), and TRA-1 (Gli transcriptional repressor), which acts both in sex determination and in physiological demand control of oogenesis, coordinating these processes. In the distal germline, where MPK-1 is not activated, TRA-1 represses the male fate as NOS-3 functions in translational repression leading to inactivation of the FEM-CUL-2 ubiquitin ligase. In the proximal germline, sperm-dependent physiological MPK-1 activation results in phosphorylation-based inactivation of NOS-3, FEM-CUL-2-mediated degradation of TRA-1 and the promotion of membrane organization during oogenesis.

Original languageEnglish (US)
Pages (from-to)677-688
Number of pages12
JournalDevelopmental Cell
Issue number5
StatePublished - May 17 2011

Bibliographical note

Funding Information:
We thank Siqun Xu for assistance in generating transgenic lines. We thank Jim Skeath for helpful comments and Edward Kipreos and lab members for helpful discussions. We thank Alessandro Puoti for the anti-FEM-3 antibody, Eric Haag for the Cb-fem-3(nm63) mutant and Karen Oegema for the anti-ANI-1 antibody. We thank WormBase and the Caenorhabditis Genetics Center for resources. This work was possible through funding from the National Institutes of Health GM085150 and GM63310 to T.S., GM053099 to D.Z., and T32HD007480 to M.B.


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