Protein Aggregation and Disaggregation in Cells and Development

J Mol Biol. 2021 Oct 15;433(21):167215. doi: 10.1016/j.jmb.2021.167215. Epub 2021 Aug 24.

Abstract

Protein aggregation is a feature of numerous neurodegenerative diseases. However, regulated, often reversible, formation of protein aggregates, also known as condensates, helps control a wide range of cellular activities including stress response, gene expression, memory, cell development and differentiation. This review presents examples of aggregates found in biological systems, how they are used, and cellular strategies that control aggregation and disaggregation. We include features of the aggregating proteins themselves, environmental factors, co-aggregates, post-translational modifications and well-known aggregation-directed activities that influence their formation, material state, stability and dissolution. We highlight the emerging roles of biomolecular condensates in early animal development, and disaggregation processing proteins that have recently been shown to play key roles in gametogenesis and embryogenesis.

Keywords: ABCF gene family; RuvBL gene family; amyloid; biomolecular condensate; chaperone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Embryonic Development / genetics*
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Gametogenesis / genetics*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Memory / physiology
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Protein Aggregates / genetics*
  • Protein Aggregation, Pathological / genetics*
  • Protein Aggregation, Pathological / metabolism
  • Protein Aggregation, Pathological / pathology
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Signal Transduction

Substances

  • ABCF1 protein, human
  • AGFG1 protein, human
  • ATP-Binding Cassette Transporters
  • Heat-Shock Proteins
  • Nuclear Pore Complex Proteins
  • Protein Aggregates
  • Protein Isoforms
  • RNA-Binding Proteins