STOP proteins.
Microtubules assembled from purified tubulin in vitro are labile, rapidly disassembling when exposed to a variety of depolymerizing conditions such as cold temperature. In contrast, in many cell types, microtubules seem to be unaffected when the cell is exposed to the cold. This resistance of microtubules to the cold has been intriguing because the earliest and by far most studied microtubule-associated proteins such as MAP2 and tau are devoid of microtubule cold stabilizing activity. Over the past several years, it has been shown that resistance of microtubules to the cold is largely due to polymer association with a class of microtubule-associated proteins called STOPs. STOPs are calmodulin-binding and calmodulin-regulated proteins which, in mammals, are encoded by a single gene but exhibit substantial cell specific variability due to mRNA splicing and alternative promoter use. STOP microtubule stabilizing activity has been ascribed to two classes of new bifunctional calmodulin- and microtubule-binding motifs, with distinct microtubule binding properties in vivo. STOPs seem to be restricted to vertebrates and are composed of a conserved domain split by the apparent insertion of variable sequences that are completely unrelated among species. Recently, STOP suppression in mice has been found to induce synaptic defects associated with neuroleptic-sensitive behavioral disorders. Thus, STOPs are important for synaptic plasticity. Additionally, STOP-deficient mice may yield a pertinent model for the study of neuroleptics in illnesses such as schizophrenia, currently thought to result from defects in synapse function.
Laboratoire du Cytosquelette, INSERM U366, DRDC/CS, CEA-Grenoble, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France. cbosc@cea.fr
Christophe
C
Bosc
Annie
A
Andrieux
Didier
D
Job
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse