WDR26 Functions as a Scaffolding Protein to Promote Gβγ-mediated Phospholipase C β2 (PLCβ2) Activation in Leukocytes

Abstract

Background: It remains unclear how G␤␥ regulates diverse effectors in cells. Results: WDR26 exists in oligomers. It simultaneously binds both G␤␥ and PLC␤2 to enhance PLC␤2 membrane translocation and activation by G␤␥ in leukocytes. Conclusion: WDR26 functions as a scaffolding protein to promote G␤␥-mediated PLC␤2 activation. Significance: These findings uncover a novel mechanism of regulating G␤␥ signaling through a scaffolding protein.

Distinct self-interaction domains promote Multi Sex Combs accumulation in and formation of theDrosophilahistone locus body

“…Other than the prediction that this domain contains α-helical regions, there is no structural information on the CTLH domain. The CTLH domains of several proteins have been shown to participate in protein–protein interactions important for the assembly of multiprotein complexes ( Kobayashi et al ., 2007 ; Menssen et al ., 2012 ; Sun et al ., 2013 ; Salemi et al ., 2014 ). The Mxc SIF domain that we identified functions similarly to the CTLH domain, but is clearly distinct from it.…”

Refinement of the critical region of 1q41q42 microdeletion syndrome identifies FBXO28 as a candidate causative gene for intellectual disability and seizures

“…The NVL gene has two isoforms, and the longer isoform, NVL2 , has been implicated in ribosome and telomerase biosynthesis [Nagahama et al, ; Her and Chung, ]. The WDR26 gene encodes a WD40 domain containing protein with roles in leukocyte activation and migration, and may also influence MAPK and apoptosis signaling [Zhu et al, ; Zhao et al, ; Sun et al, ]. The MIR320B2 locus is a microRNA of unknown function.…”

Structural Insights into Phospholipase C-βFunction

“…An intriguing possibility is that the distal CTD could also influence the membrane association of the catalytic core by inducing differences in local membrane curvature. An additional layer of regulatory complexity arises from the observation that PLCb isozymes interact with numerous scaffolding proteins to form signaling complexes (Cai et al, 2005;Cartier et al, 2011;Sun et al, 2013). How these higher order complexes contribute to PLCb regulation and whether they alter activation by Ga q , Gbg, and small GTPases are not understood, and represent the next frontier for structure/function analyses of PLCb enzymes.…”

“…Members of the Rho family of small molecular weight G proteins, such as the Rac isoforms, also directly bind and activate PLCb, linking PLCb activity to GPCR-independent signaling cascades (Gresset et al, 2012;Kadamur and Ross, 2013). It is also increasingly recognized that the membrane itself plays a role in the regulation of PLCb, as may interactions with scaffolding proteins (Cartier et al, 2011;Grubb et al, 2011Grubb et al, , 2012Sun et al, 2013). In this review, we highlight the current understanding of the molecular basis of regulation of mammalian PLCb enzymes and their modulation by small molecules, with an emphasis on recent structural discoveries.…”