Drosophila Schip1 Links Expanded and Tao-1 to Regulate Hippo Signaling

Abstract

Regulation of organ size is essential in animal development, and Hippo (Hpo) signaling is a major conserved mechanism for controlling organ growth. In Drosophila, Hpo and Warts kinases are core components of this pathway and function as tumor suppressors by inhibiting Yorkie (Yki). Expanded (Ex) is a regulator of the Hpo activity, but how they are linked is unknown. Here, we show that Schip1, a Drosophila homolog of the mammalian Schwannomin interacting protein 1 (SCHIP1), provides a link between Ex and Hpo. Ex is required for apical localization of Schip1 in imaginal discs. Schip1 is necessary for promoting membrane localization and phosphorylation of Hpo by recruiting the Hpo kinase Tao-1. Taking these findings together, we conclude that Schip1 directly links Ex to Hpo signaling by recruiting Tao-1. This study provides insights into the mechanism of Tao-1 regulation and a potential growth control function for SCHIP1 in mammals.

Schip1, a new upstream regulator of Hippo signaling

“…4 Similar phenomena have also been seen in ex mutant organs. Several upstream regulators of Hippo signaling including Crb, Ex and Schip1 are localized to the apical membrane.…”

“…Importantly, Schip1 is directly involved in linking Ex and Tao-1 kinase. 4 Schip1 partially co-localizes with Ex to the apical cell membranes in an Ex-dependent manner. Further, Schip1 is required for the localization of cytoplasmic Tao-1 kinase to the cell membrane to promote the Hpo function.…”

A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster

“…In addition to discovering the key substrate(s) of Trc in trachea, defining modes of upstream regulation of Tao-1 activity should provide insights into how this Hippo-like signaling module controls tube development. One candidate upstream regulator is Schip1, which has been linked to Tao-1 and the Hippo pathway in the context of organ size control (Chung et al, 2016), although the mechanism by which it functions is unclear.…”

Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network

“…In mammalian cells, βPix was identified as interacting with LATS and YAP/TAZ to stimulate YAP/TAZ phosphorylation [40]. Schip1 was recently identified in Drosophila as a protein that activates Hpo by binding to both Expanded and Tao-1 [41], a kinase that induces Hpo [42, 43]. …”