Cingulin and paracingulin tether myosins-2 to junctions to mechanoregulate the plasma membraneстатья
Статья опубликована в высокорейтинговом журнале
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 17 апреля 2024 г.
Аннотация:The mechanisms that regulate the spatial sorting of nonmuscle myosins-2 (NM2) isoforms and couple them mechanically tothe plasma membrane are unclear. Here we show that the cytoplasmic junctional proteins cingulin (CGN) and paracingulin(CGNL1) interact directly with NM2s through their C-terminal coiled-coil sequences. CGN binds strongly to NM2B, and CGNL1to NM2A and NM2B. Knockout (KO), exogenous expression, and rescue experiments with WT and mutant proteins show thatthe NM2-binding region of CGN is required for the junctional accumulation of NM2B, ZO-1, ZO-3, and phalloidin-labeled actinfilaments, and for the maintenance of tight junction membrane tortuosity and apical membrane stiffness. CGNL1 expressionpromotes the junctional accumulation of both NM2A and NM2B and its KO results in myosin-dependent fragmentation ofadherens junction complexes. These results reveal a mechanism for the junctional localization of NM2A and NM2B and indicatethat, by binding to NM2s, CGN and CGNL1 mechanically couple the actomyosin cytoskeleton to junctional protein complexesto mechanoregulate the plasma membrane.