DOI: 10.4231/zmjz-pm07
title: RhoA allosterically activates phospholipase Cepsilon via its EF hands

description: &lt;p&gt;&lt;span style="font-size:medium"&gt;&lt;span style="font-family:Aptos, sans-serif"&gt;&lt;span style="color:#000000"&gt;&lt;span style="font-style:normal"&gt;&lt;span style="font-weight:400"&gt;&lt;span style="white-space:normal"&gt;&lt;span style="text-decoration:none"&gt;&lt;span style="line-height:32px"&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt;Phospholipase C&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt; (PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt;) cleaves phosphatidylinositol lipids to increase intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; and activate protein kinase C (PKC) in response to stimulation of cell surface receptors. PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt; is activated via direct binding of small GTPases at the cytoplasmic leaflets of cellular membranes. In the cardiovascular system, the RhoA GTPase regulates PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt; to initiate a pathway that protects against ischemia/reperfusion injuries, but the underlying molecular mechanism is not known. We present here the cryo-electron microscopy (cryo-EM) reconstruction of RhoA bound to PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt;, showing that the G protein binds a unique insertion within the PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt; EF hands. Deletion of or mutations to this PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt; insertion decrease RhoA-dependent activation without impacting regulation by other G proteins. Together, our data support a model wherein RhoA binding to PLC&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Symbol"&gt;&lt;span style="color:black"&gt;e&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="line-height:29.333336px"&gt;&lt;span style="font-family:Arial, sans-serif"&gt;&lt;span style="color:black"&gt; allosterically activates the lipase and increases its interactions with the membrane, resulting in maximum activity and cardiomyocyte survival. &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
description: Source data (assay, western blot, cryo-EM) for this manuscript.