MOLECULAR CHAPERONES AND THE CYTOSKELETON

Heat shock proteins, first observed because they are preferentially sy nthesized by organisms exposed to heat or other physiological stress, are also synthesized constitutively, These proteins are divided into s everal families, namely, HSP100, 90, 70, 60 (chaperonin), and the smal l heat shock/alpha-crystallin proteins, They enjoy a wide phylogenetic distribution and are important because they function as molecular cha perones, able to mediate many cellular processes through an influence on higher order protein structure. For example, molecular chaperones a ssist in the transport of proteins into mitochondria and chloroplasts, as well as influencing clathrin lattice dynamics, viral replication a nd transcriptional activation, Under conditions of stress, some molecu lar chaperones prevent denaturation of proteins while others may disso ciate protein aggregates, refolding monomers derived therefrom or dire cting their proteolytic destruction, We present in this review an anal ysis 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 com plex as the eukaryotic cytoplasmic chaperonin which directs folding of cytoskeletal proteins such as alpha/beta/gamma-tubulin, actin and cen tractin, Moreover, the TCP-1 complex is a centrosomal component, appar ently involved in the nucleation of microtubules. Other molecular chap erones recognize one or more cytoskeletal elements and in most cases t hey modulate the assembly of and/or provide protection for their const ituent proteins, For example, HSP70 protects the centrosome and perhap s intermediate filaments during heat shock, and like HSP90; it binds t o microtubules. Small heat shock proteins interact with microfilaments and intermediate filaments, affect their polymerization and guard the m from heat shock by a phosphorylation-dependent mechanism. We conclud e that molecular chaperones have different but cooperative roles in th e formation and function of the eukaryotic cell cytoskeleton.