Stathmin and its Phosphoprotein Family. General Properties, Biochemical and Functional Interaction with Tubulin.

Abstract

Stathmin, also referred to as Op18, is a ubiquitous cytosolic phosphoprotein, proposed to be a small regulatory protein and a relay integrating diverse intracellular signaling pathways involved in the control of cell proliferation, differentiation and activities. It interacts with several putative downstream target and/or partner proteins. One major action of stathmin is to interfere with microtubule dynamics, by inhibiting the formation of microtubules and/or favoring their depolymerization. Stathmin (S) interacts directly with soluble tubulin (T), which results in the formation of a T2S complex which sequesters free tubulin and therefore impedes microtubule formation. However, it has been also proposed that stathmin's action on microtubules might result from the direct promotion of catastrophes, which is still controversial. Phosphorylation of stathmin regulates its biological actions: it reduces its affinity for tubulin and hence its action on microtubule dynamics, which allows for example progression of cells through mitosis. Stathmin is also the generic element of a protein family including the neural proteins SCG10, SCLIP and RB3/RB3'/RB3". Interestingly, the stathmin-like domains of these proteins also possess a tubulin binding activity in vitro. In vivo, the transient expression of neural phosphoproteins of the stathmin family leads to their localization at Golgi membranes and, as previously described for stathmin and SCG10, to the depolymerization of interphasic microtubules. Altogether, the same mechanism for microtubule destabilization, that implies tubulin sequestration, is a common feature likely involved in the specific biological roles of each member of the stathmin family.

Stathmin reveals dissociable roles of the basolateral amygdala in parental and social behaviors

“…This is consistent with the previous work that has shown that stathmin Ϫ/Ϫ mice are deficient in amygdala-dependent innate and learned fear, but are normal in hippocampus-dependent spatial memory (13). At the cellular level, stathmin is a negative regulator of microtubule formation (25) and in the amygdala of stathmin Ϫ/Ϫ mice a decrease in microtubule dynamics leads to deficits in synaptic plasticity (13), suggesting that the deficiency at the BLA synapses may be responsible for effects described here.…”

SCLIP Is Crucial for the Formation and Development of the Purkinje Cell Dendritic Arbor

“…Stathmin family phosphoproteins including stathmin, SCG10, SCLIP, and RB3, have been proposed to play specific and complementary roles in the formation and maturation of the nervous system (Ozon et al, 1997(Ozon et al, , 1998Curmi et al, 1999). They have been originally identified for their capacity to integrate and relay intracellular signaling pathways (Sobel, 1991), at least in part through tubulin binding and the control of microtubule dynamics (Belmont and Mitchison, 1996;Curmi et al, 1997;Steinmetz et al, 2000;Charbaut et al, 2001;Ravelli et al, 2004).…”

Reduced Stathmin-1 Expression in Natural Killer Cells Associated with Spontaneous Abortion

“…It is highly conserved among vertebrates and is associated with tubulin binding and microtubule destabilization. 1,2 Stathmin-1 has a complex phosphorylation pattern in response to various extracellular signals, in particular growth and differentiation factors. 3 Moreover, stathmin-1 phosphorylation varies during the cell cycle.…”