The plasma membrane: penultimate regulator of ADAM sheddase function

Publication date: Available online 15 June 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Author(s): Karina Reiss, Sucharit Bhakdi Background ADAM10 and ADAM17 are the best characterized members of the ADAM (A Disintegrin and Metalloproteinase) – family of transmembrane proteases. Both are involved diverse physiological and pathophysiological processes. ADAMs are known to be regulated by posttranslational mechanisms. However, emerging evidence indicates that the plasma membrane with its unique dynamic properties may additionally play an important role in controlling sheddase function. Scope of review Membrane events that could contribute to regulation of ADAM-function are summarized. Major conclusions Surface expression of peptidolytic activity should be differentiated from ADAM-sheddase function since the latter additionally requires that the protease finds its substrate in the lipid bilayer. We propose that this is achieved through horizontal and vertical reorganization of membrane nanoarchitecture coordinately occurring at the sites of sheddase activation. Reshuffling of nanodomains thereby guides traffic of enzyme and substrate to each other. For ADAM17 phosphatidylserine exposure is required to then induce its shedding function. General significance The novel concept that physicochemical properties of the lipid bilayer govern the action of ADAM-proteases may be extendable to other functional proteins that act at the cell surface.

Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - June 16, 2017 Category: Molecular Biology Source Type: research