Contribution of the Presenilins in the cell biology, structure and function of γ-secretase.

Seminars in Cell & Developmental Biology
Abril Escamilla-AyalaWim Annaert

Abstract

γ-Secretase cleavage is essential for many biological processes and its dysregulation is linked to disease, including cancer and Alzheimer's disease. Therefore, understanding the regulation of its activity is of major importance to improve drug design and develop novel therapeutics. γ-Secretase belongs to the family of intramembrane cleaving proteases (i-CLiPs), which cleaves its substrates in a process termed regulated intramembrane proteolysis (RIP). During RIP, type-I transmembrane proteins are first cleaved within their ectodomain by a sheddase and then within their transmembrane domain by γ-secretase. γ-Secretase is composed of four integral membrane proteins that are all essential for its function: presenilin (PSEN), anterior pharynx defective 1 (APH1), nicastrin (NCT) and presenilin enhancer 2 (PEN-2). Given the presence of two PSEN homologues (PSEN1 & 2) and several APH1 isoforms, a heterogeneity exists in cellular γ-secretase complexes. It is becoming clear that each of these complexes has overlapping as well as distinct biological characteristics. This review summarizes our current knowledge on complex formation, trafficking, subcellular localization, interactors and the structure of γ-secretase, with a focus, when po...Continue Reading

Citations

Jul 1, 2020·The Cerebellum·Yury SeliverstovSergey Illarioshkin
Aug 18, 2020·Journal of Alzheimer's Disease : JAD·Carol A Deaton, Gail V W Johnson
Sep 3, 2020·Journal of Cell Science·Wim Annaert, Christoph Kaether
Mar 5, 2021·The Journal of Biological Chemistry·Frédéric CheclerInger Lauritzen
Mar 2, 2021·Neural Regeneration Research·Eleonora NardiniGilbert Bernier
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Jul 23, 2021·The Journal of Cell Biology·Rosanne WoutersWim Annaert
Aug 16, 2021·Ageing Research Reviews·Zoë P Van AckerWim Annaert

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