Abstract:
:Shroom (Shrm) proteins are essential regulators of cell shape and tissue morpho-logy during animal development that function by interacting directly with the coiled-coil region of Rho kinase (Rock). The Shrm-Rock interaction is sufficient to direct Rock subcellular localization and the subsequent assembly of contractile actomyosin networks in defined subcellular locales. However, it is unclear how the Shrm-Rock interaction is regulated at the molecular level. To begin investigating this issue, we present the structure of Shrm domain 2 (SD2), which mediates the interaction with Rock and is required for Shrm function. SD2 is a unique three-segmented dimer with internal symmetry, and we identify conserved residues on the surface and within the dimerization interface that are required for the Rock-Shrm interaction and Shrm activity in vivo. We further show that these residues are critical in both vertebrate and invertebrate Shroom proteins, indicating that the Shrm-Rock signaling module has been functionally and molecularly conserved. The structure and biochemical analysis of Shrm SD2 indicate that it is distinct from other Rock activators such as RhoA and establishes a new paradigm for the Rock-mediated assembly of contractile actomyosin networks.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Mohan S,Rizaldy R,Das D,Bauer RJ,Heroux A,Trakselis MA,Hildebrand JD,VanDemark APdoi
10.1091/mbc.E11-11-0937subject
Has Abstractpub_date
2012-06-01 00:00:00pages
2131-42issue
11eissn
1059-1524issn
1939-4586pii
mbc.E11-11-0937journal_volume
23pub_type
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