Stathmin and its phosphoprotein family: General properties, biochemical and functional interaction with tubulin

Stathmin, also referred to as Op18, is a ubiquitous cytosolic phosphoprotei n, proposed to be a small regulatory protein and a relay integrating divers e intracellular signaling pathways involved in the control of cell prolifer ation, differentiation and activities. It interacts with several putative d ownstream target and/or partner proteins. One major action of stathmin is t o interfere with microtubule dynamics, by inhibiting the formation of micro tubules and/or favoring their depolymerization. Stathmin (S) interacts dire ctly with soluble tubulin (T), which results in the formation of a T2S comp lex which sequesters free tubulin and therefore impedes microtubule formati on. However, it has been also proposed that stathmin's action on microtubul es might result from the direct promotion of catastrophes, which is still c ontroversial. Phosphorylation of stathmin regulates its biological actions: it reduces its affinity for tubulin and hence its action on microtubule dy namics, which allows for example progression of cells through mitosis. Stathmin is also the generic element of a protein family including the neur al proteins SCG10, SCLIP and RB3/RB3'/RB3 ". Interestingly, the stathmin-li ke domains of these proteins also possess a tubulin binding activity in vit ro. In vivo, the transient expression of neural phosphoproteins of the stat hmin family leads to their localization at Golgi membranes and, as previous ly described for stathmin and SCG10, to the depolymerization of interphasic microtubules. Altogether, the same mechanism for microtubule destabilizati on, that implies tubulin sequestration, is a common feature likely involved in the specific biological roles of each member of the stathmin family.