Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein

Jin Gyeong Park, Hanul Jeon, Kwang Yeon Hwang, Sun Shin Cha, Rafael T. Han, Hyesung Cho, In Gyun Lee

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)827-835
Number of pages9
JournalExperimental and Molecular Medicine
Volume56
Issue number4
DOIs
Publication statusPublished - 2024 Apr

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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