Karina Reiss1, Sucharit Bhakdi2. 1. Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany. Electronic address: kreiss@dermatology.uni-kiel.de. 2. Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
Abstract
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. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.
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. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.
Authors: Inmaculada Lopez-Font; Claudia P Boix; Henrik Zetterberg; Kaj Blennow; Javier Sáez-Valero Journal: Mol Neurobiol Date: 2019-07-09 Impact factor: 5.590
Authors: Beiyu Tang; Xue Li; Thorsten Maretzky; Jose Manuel Perez-Aguilar; David McIlwain; Yifang Xie; Yufang Zheng; Tak W Mak; Harel Weinstein; Carl P Blobel Journal: FASEB J Date: 2020-02-26 Impact factor: 5.191
Authors: O Verdejo-Torres; C Flores-Maldonado; T Padilla-Benavides; J P Campos-Blázquez; I Larré; R Lara-Lemus; E Perez Salazar; M Cereijido; R G Contreras Journal: J Membr Biol Date: 2019-04-30 Impact factor: 1.843
Authors: Daniela Kugelmann; Maresa Anders; Anna M Sigmund; Desalegn T Egu; Ramona A Eichkorn; Amir S Yazdi; Miklós Sárdy; Michael Hertl; Dario Didona; Takashi Hashimoto; Jens Waschke Journal: Front Immunol Date: 2022-06-30 Impact factor: 8.786