Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein.

Autor: Park JG; Biomedical Research Division, Korea Institute of Science and Technology, Seoul, 02792, South Korea.; Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea., Jeon H; Biomedical Research Division, Korea Institute of Science and Technology, Seoul, 02792, South Korea.; Department of Chemistry & Nanoscience, Ewha Womans University, Seoul, 03760, South Korea., Hwang KY; Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea., Cha SS; Department of Chemistry & Nanoscience, Ewha Womans University, Seoul, 03760, South Korea., Han RT; Biomedical Research Division, Korea Institute of Science and Technology, Seoul, 02792, South Korea.; KHU-KIST Department of Converging Science and Technology, Kyunghee University, Seoul, 02447, South Korea., Cho H; Extreme Materials Research Center, Korea Institute of Science and Technology, Seoul, 02792, South Korea., Lee IG; Biomedical Research Division, Korea Institute of Science and Technology, Seoul, 02792, South Korea. ik86@kist.re.kr.; Department of Biological Chemistry, University of Science and Technology, Daejeon, 34113, South Korea. ik86@kist.re.kr.
Jazyk: angličtina
Zdroj: Experimental & molecular medicine [Exp Mol Med] 2024 Apr; Vol. 56 (4), pp. 827-835. Date of Electronic Publication: 2024 Apr 01.
DOI: 10.1038/s12276-024-01200-7
Abstrakt: Intracellular retrograde transport in eukaryotic cells relies exclusively on the molecular motor cytoplasmic dynein 1. Unlike its counterpart, kinesin, dynein has a single isoform, which raises questions about its cargo specificity and regulatory mechanisms. The precision of dynein-mediated cargo transport is governed by a multitude of factors, including temperature, phosphorylation, the microtubule track, and interactions with a family of activating adaptor proteins. Activating adaptors are of particular importance because they not only activate the unidirectional motility of the motor but also connect a diverse array of cargoes with the dynein motor. Therefore, it is unsurprising that dysregulation of the dynein-activating adaptor transport machinery can lead to diseases such as spinal muscular atrophy, lower extremity, and dominant. Here, we discuss dynein motor motility within cells and in in vitro, and we present several methodologies employed to track the motion of the motor. We highlight several newly identified activating adaptors and their roles in regulating dynein. Finally, we explore the potential therapeutic applications of manipulating dynein transport to address diseases linked to dynein malfunction.
(© 2024. The Author(s).)
Databáze: MEDLINE
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