Fig. 3.

Hsp40-Hsc70-dependent pathway for the biogenesis of tail-anchored proteins at the ER. General chaperones of the heat-shock family can accept and shield tail-anchored proteins with a TM segment of relatively low hydrophobicity (Rabu et al., 2008), presumably preventing their aggregation. This interaction might simply enable the subsequent unassisted integration of the TM segment by direct partitioning into the lipid bilayer, or allow a similar process for which a dedicated ER-membrane receptor is a prerequisite. No such receptor has been identified to date and, similarly, any role for an integrase during the Hsp40-Hsc70 pathway for biogenesis of tail-anchored proteins remains hypothetical.