Ancestral roles of the Fam20C family of secreted protein kinases revealed in C. Elegans

Adina Gerson-Gurwitz, Carolyn A. Worby, Kian Yong Lee, Renat Khaliullin, Jeff Bouffard, Dhanya Cheerambathur, Karen Oegema, Erin J. Cram, Jack E. Dixon, Arshad Desai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Fam20C is a secreted protein kinase mutated in Raine syndrome, a human skeletal disorder. In vertebrates, bone and enamel proteins are major Fam20C substrates. However, Fam20 kinases are conserved in invertebrates lacking bone and enamel, suggesting other ancestral functions. We show that FAMK-1, the Caenorhabditis elegans Fam20C orthologue, contributes to fertility, embryogenesis, and development. These functions are not fulfilled when FAMK-1 is retained in the early secretory pathway. During embryogenesis, FAMK-1 maintains intercellular partitions and prevents multinucleation; notably, temperature elevation or lowering cortical stiffness reduces requirement for FAMK-1 in these contexts. FAMK-1 is expressed in multiple adult tissues that undergo repeated mechanical strain, and selective expression in the spermatheca restores fertility. Informatic, biochemical, and functional analysis implicate lectins as FAMK-1 substrates. These findings suggest that FAMK-1 phosphorylation of substrates, including lectins, in the late secretory pathway is important in embryonic and tissue contexts where cells are subjected to mechanical strain.

Original languageEnglish
Pages (from-to)3795-3811
Number of pages17
JournalJournal of Cell Biology
Issue number11
Publication statusPublished - 20 Sept 2019


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