There and back again: Intracellular trafficking, release and recycling of matrix metalloproteinases
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There and back again: Intracellular trafficking, release and recycling of matrix metalloproteinases. / Hey, Sven; Ratt, Artur; Linder, Stefan.
in: BBA-MOL CELL RES, Jahrgang 1869, Nr. 4, 119189, 04.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - There and back again: Intracellular trafficking, release and recycling of matrix metalloproteinases
AU - Hey, Sven
AU - Ratt, Artur
AU - Linder, Stefan
N1 - Copyright © 2021. Published by Elsevier B.V.
PY - 2022/4
Y1 - 2022/4
N2 - Matrix metalloproteinases are a family of zinc-dependent endopeptidases that are involved in a large variety of proteolytic processes in physiological and pathological scenarios, including immune cell surveillance, tissue homeostasis, or tumor cell metastasis. This is based on their ability to cleave a plethora of substrates that include components of the extracellular matrix, but also cell surface-associated and intracellular proteins. Accordingly, a tight regulatory web has evolved that closely regulates spatiotemporal activity of specific MMPs. An often underappreciated mechanism of MMP regulation involves their trafficking to and from specific subcellular sites that require MMP activity only for a certain period. In this review, we focus on the current knowledge of MMP intracellular trafficking, their secretion or surface exposure, as well as their recycling back from the cell surface. We discuss molecular mechanisms that enable these steps, in particular microtubule-dependent motility of vesicles that is driven by molecular motors and directed by vesicle regulatory proteins. Finally, we also point out open questions in the field of MMP motility that may become important in the future.
AB - Matrix metalloproteinases are a family of zinc-dependent endopeptidases that are involved in a large variety of proteolytic processes in physiological and pathological scenarios, including immune cell surveillance, tissue homeostasis, or tumor cell metastasis. This is based on their ability to cleave a plethora of substrates that include components of the extracellular matrix, but also cell surface-associated and intracellular proteins. Accordingly, a tight regulatory web has evolved that closely regulates spatiotemporal activity of specific MMPs. An often underappreciated mechanism of MMP regulation involves their trafficking to and from specific subcellular sites that require MMP activity only for a certain period. In this review, we focus on the current knowledge of MMP intracellular trafficking, their secretion or surface exposure, as well as their recycling back from the cell surface. We discuss molecular mechanisms that enable these steps, in particular microtubule-dependent motility of vesicles that is driven by molecular motors and directed by vesicle regulatory proteins. Finally, we also point out open questions in the field of MMP motility that may become important in the future.
U2 - 10.1016/j.bbamcr.2021.119189
DO - 10.1016/j.bbamcr.2021.119189
M3 - SCORING: Review article
C2 - 34973301
VL - 1869
JO - BBA-MOL CELL RES
JF - BBA-MOL CELL RES
SN - 0167-4889
IS - 4
M1 - 119189
ER -