Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein

Authors
Park, Jin-GyeongJeon, HanulHwang, Kwang YeonCha, Sun-ShinHan, Rafael T.Cho, HyesungLee, In-Gyun
Issue Date
2024-04
Publisher
Springer Nature
Citation
Experimental & Molecular Medicine, v.56, pp.827 - 835
Abstract
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. This research examines how parts move within a specific type of cell, called eukaryotic cells, focusing on the role of a component called cytoplasmic dynein 1 in moving various items. However, understanding dynein's function is difficult due to its complexity and the systems that control it. Recent progress in structural, biophysical (relating to the physical properties of biological molecules), and cellular methods are helping us understand these processes. The research also looks at dynein's role in human diseases, especially neurodegenerative diseases, and the possibility of using this knowledge for treatment. The scientists emphasize the need for more research into dynein's molecular structure and the potential treatment possibilities this research could offer.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
Keywords
SPINAL MUSCULAR-ATROPHY; LOWER-EXTREMITY PREDOMINANCE; MICROTUBULE-BASED TRANSPORT; ORGANELLE TRANSPORT; CLINICAL SPECTRUM; MULTIPLE-MODES; MOTOR-ADAPTER; MUTATIONS; DYNACTIN; BICD2
ISSN
1226-3613
URI
https://pubs.kist.re.kr/handle/201004/149687
DOI
10.1038/s12276-024-01200-7
Appears in Collections:
KIST Article > 2024
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