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Activation and Regulation of Cytoplasmic Dynein

John T Canty1, Ahmet Yildiz2

  • 1Biophysics Graduate Group, University of California at Berkeley, Berkeley, CA 94720, USA.

Trends in Biochemical Sciences
|April 21, 2020
PubMed

Insights

Cytoplasmic dynein, a motor protein, is activated for intracellular transport when it forms a complex with dynactin and adaptors, a process aided by Lis1. This explains its crucial role in cellular functions.

Area of Science:

  • Cell Biology
  • Molecular Motors
  • Cytoskeletal Dynamics

Background:

  • Cytoplasmic dynein is a key AAA+ motor protein responsible for minus-end directed microtubule transport of intracellular cargoes.
  • Previously, isolated dynein was considered a weak and slow motor, exhibiting diffusive movement on microtubules.
  • Recent findings indicate dynein exists in an autoinhibited state, requiring activation for processive motility.

Purpose of the Study:

  • To review the mechanisms of cytoplasmic dynein activation and regulation.
  • To explain the role of dynactin, cargo adaptors, and Lis1 in dynein-mediated transport.
  • To provide insights into why Lis1 is essential for most dynein-driven cellular processes.

Main Methods:

  • Literature review of in vitro and in vivo studies on cytoplasmic dynein.
  • Analysis of structural and functional data regarding dynein-dynactin-adaptor complexes.
  • Integration of findings on the role of accessory proteins like Lis1.

Main Results:

  • Dynein motility is significantly enhanced through the formation of a ternary complex with dynactin and cargo adaptors.
  • Lis1 facilitates the efficient assembly of this functional dynein complex.
  • This complex formation overcomes dynein's autoinhibited state, enabling processive movement.

Conclusions:

  • Cytoplasmic dynein requires specific cofactors, including dynactin and cargo adaptors, for efficient and processive motility.
  • Lis1 acts as a crucial activator, promoting the assembly of the functional dynein motor complex.
  • Understanding these regulatory mechanisms is vital for comprehending intracellular transport and cellular functions dependent on dynein.
Keywords:
Lis1cargo adaptorscytoskeletondynactindyneinintracellular transportmotor proteins

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