Membrane insertion of Cavin1 facilitates caveolae assembly
Caveolae are small cell surface invaginations, important for control of membrane tension, signaling cascades and lipid sorting. Their formation is coupled to the lipid-dependent oligomerization of the proteins Caveolin1 and Cavin1, which are essential for membrane curvature generation. Yet, the mechanistic understanding of how Cavin1 assembles at the membrane interface is lacking. Here, we used model membranes combined with biophysical techniques to show that Cavin1 inserts into membranes. We found that the helical region 1 (HR1) initiated membrane binding via electrostatic interactions, which is further enforced by partial helical insertion in a PI(4,5)P2-dependent process mediated by the disordered region 1 (DR1). In agreement with this, the DR1 was found important for the co-assembly of Cavin1 with Caveolin1 in living cells. We propose that DR1 and HR1 of Cavin1 constitute a novel membrane interacting unit facilitating dynamic rounds of assembly and disassembly of Cavin1 at the membrane.