β-H-Spectrin is a key component of an apical-medial hub of proteins during cell wedging in tube morphogenesis

Gillard, G.; Röper, K.

doi:10.1101/2023.12.05.570290

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bioRxiv · 10.1101/2023.12.05.570290

β-H-Spectrin is a key component of an apical-medial hub of proteins during cell wedging in tube morphogenesis

Gillard, G.·Röper, K.

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Abstract

Coordinated cell shape changes are a major driver of tissue morphogenesis during development, with apical constriction or wedging of groups of epithelial cells for instance leading to tissue bending in folding or budding processes. During the budding of the tubes of the salivary glands in the Drosophila embryo we previously identified a key interplay between the apical-medial actomyosin that drives apical constriction with the underlying longitudinal microtubule array. At this microtubule-actomyosin interface a hub of proteins accumulates: in addition to the microtubule-actin crosslinker Shot and the minus-end-binder Patronin, we identified two actin-crosslinkers, {beta}-H-Spectrin and Filamin, and the multi-PDZ protein Big bang as components of this apical-medial hub. Tissue-specific degradation of {beta}-H-Spectrin led to reduction of apical-medial Big bang, F-actin, Shot and Patronin and concomittant defects in apical constriction and tube morphogenesis. Residual Patronin still present in the apical-medial position was sufficient to assist microtubule reorganisation into the longitudinal array. In contrast to Patronin and Shot, neither {beta}-H-Spectrin nor Big bang required microtubules for their localisation. {beta}-H-Spectrin instead appeared to be recruited to the apical-medial domain via binding to phosphoinositides that accumulated here. Overexpression of a {beta}-H-Spectrin fragment containing its PH domain displaced endogenous {beta}-H-Spectrin from the apical-medial domain and led to strong morphogenetic defects. The interconnected hub therefore required the synergy of membrane-associated {beta}-H-Spectrin and microtubules and their respective interactors for its assembly and function in sustaining the apical constriction during tube invagination.

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Gillard, G., Röper, K.. 2023-12-05. β-H-Spectrin is a key component of an apical-medial hub of proteins during cell wedging in tube morphogenesis. https://doi.org/10.1101/2023.12.05.570290

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