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Publication : Rack1 regulates cellular patterning and polarity in the mouse cochlea.

First Author  Yu D Year  2022
Journal  Exp Cell Res Volume  421
Issue  2 Pages  113387
PubMed ID  36252648 Mgi Jnum  J:330677
Mgi Id  MGI:7380095 Doi  10.1016/j.yexcr.2022.113387
Citation  Yu D, et al. (2022) Rack1 regulates cellular patterning and polarity in the mouse cochlea. Exp Cell Res 421(2):113387
abstractText  Rack1 features seven WD40 repeats that fold into a multifaceted scaffold used to build signaling complexes in a context-dependent manner. Previous in vitro studies have revealed associations between Rack1 and many other proteins. Rack 1 is required for establishing planar cell polarity (PCP) in zebrafish and Xenopus. However, any molecular role of Rack1 in protein complexes or polarity regulation remains unclear. Here, we show that Rack1 is an essential gene in mice. Conditional knockout of Rack1 shortened the cochlear duct and induced cellular patterning defects characteristic of defective convergent extension (this PCP process is mediated by cellular junctional remodeling in the developing cochlear epithelium). Also, cochlear hair cells were no longer uniformly oriented in Rack1 conditional knockout mutants. Rack1 was enriched in the cellular cortices of sensory hair cells. In Rack1-deficient cochleae, E-cadherin expression at the cellular boundaries was greatly reduced. Together, the findings reveal a molecular role of Rack1 in PCP signaling that likely involves modulation of E-cadherin levels at the adherens junctions of the plasma membrane.
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