Stathmin Family Proteins Display Specific Molecular and Tubulin Binding Properties

Abstract

Stathmin family phosphoproteins (stathmin, SCG10, SCLIP, and RB3/RB3/RB3؆) are involved in signal transduction and regulation of microtubule dynamics. With the exception of stathmin, they are expressed exclusively in the nervous system, where they display different spatio-temporal and functional regulations and hence play at least partially distinct and possibly complementary roles in relation to the control of development, plasticity, and neuronal activities. At the molecular level, each possesses a specific "stathmin-like domain" and, with the exception of stathmin, various combinations of N-terminal extensions involved in their association with intracellular membrane compartments. We show here that each stathmin-like domain also displays specific biochemical and tubulin interaction properties. They are all able to sequester two ␣ /␤ tubulin heterodimers as revealed by their inhibitory action on tubulin polymerization and by gel filtration. However, they differ in the stabilities of the complexes formed as well as in their interaction kinetics with tubulin followed by surface plasmon resonance as follows: strong stability and slow kinetics for RB3; medium for SCG10, SCLIP, and stathmin; and weak stability and rapid kinetics for RB3. These results suggest that the fine-tuning of their stathmin-like domains contributes to the specific functional roles of stathmin family proteins in the regulation of microtubule dynamics within the various cell types and subcellular compartments of the developing or mature nervous system.

Variations in the colchicine-binding domain provide insight into the structural switch of tubulin

“…Tubulin concentrations were deduced from its absorbance ( 278 ϭ 1.2 mL cm Ϫ1 mg Ϫ1 ), assuming the molecular weight of the heterodimer is 100 kDa (25). The RB3 stathmin like domain (RB3-SLD) was expressed and purified as described (26). RB3-SLD concentration was determined by amino acid analysis or by titrating a known tubulin solution with RB3-SLD on a gel filtration column (Superose 12 10/300; Amersham).…”

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

“…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). Whereas stathmin is ubiquitous and cytosolic, the other proteins are essentially expressed in the nervous system and localized at the Golgi complex and vesicular structures along neurite shafts and in growth cones (Di Paolo et al, 1997; Gavet et al, 2002;Charbaut et al, 2005).…”

Stathmin/Op18 is a novel mediator of vinblastine activity

“…Over the past several decades, significant advancements have been made in our understanding of the mechanism of action of stabilizing MAPs, such as Tau [1][2][3][4]. More recently, however, attention has turned to a family of destabilizing molecules: stathmin and its family members that share the same SLD (stathmin like domain), such as RB3 [5].…”