Molecular chaperones and the cytoskeleton.
Heat shock proteins, first observed because they are preferentially synthesized by organisms exposed to heat or other physiological stress, are also synthesized constitutively. These proteins are divided into several families, namely, HSP100, 90, 70, 60 (chaperonin), and the small heat shock/alpha-crystallin proteins. They enjoy a wide phylogenetic distribution and are important because they function as molecular chaperones, able to mediate many cellular processes through an influence on higher order protein structure. For example, molecular chaperones assist in the transport of proteins into mitochondria and chloroplasts, as well as influencing clathrin lattice dynamics, viral replication and transcriptional activation. Under conditions of stress, some molecular chaperones prevent denaturation of proteins while others may dissociate protein aggregates, refolding monomers derived therefrom or directing their proteolytic destruction. We present in this review an analysis of the emerging literature on the relationship between molecular chaperones and the cytoskeleton, a collection of polymeric structures consisting of microtubules, microfilaments and intermediate filaments. A recent development in this field is identification of the TCP-1 complex as the eukaryotic cytoplasmic chaperonin which directs folding of cytoskeletal proteins such as alpha/beta/gamma-tubulin, actin and centractin. Moreover, the TCP-1 complex is a centrosomal component, apparently involved in the nucleation of microtubules. Other molecular chaperones recognize one or more cytoskeletal elements and in most cases they modulate the assembly of and/or provide protection for their constituent proteins. For example, HSP70 protects the centrosome and perhaps intermediate filaments during heat shock, and like HSP90, it binds to microtubules. Small heat shock proteins interact with microfilaments and intermediate filaments, affect their polymerization and guard them from heat shock by a phosphorylation-dependent mechanism. We conclude that molecular chaperones have different but cooperative roles in the formation and function of the eukaryotic cell cytoskeleton.
Liang
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Department of Biology, Dalhousie University, Halifax, NS, Canada.
MacRae
T H
TH
D000199:Actins / Q000378:metabolism; D000818:Animals; D018385:Centrosome / Q000378:metabolism; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D017510:Protein Folding
D000199:Actins; D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins