How Does Stathmin Destabilize Microtubules?A Root of Consciousness and Alzheimer’s Disease
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2017, Vol 1, Issue 5
Abstract
Alzheimer’s disease due to dementia and the memory brain that might be related to the microtubules disorder interrupt daily life. Alzheimer’s is a brain disease that causes a slow decline in concentrations, memory, thinking and reasoning skills. By this research we exhibited the important rules of stathmin destabilize microtubules as a root of this problem in view point of chemical molecular engineering. Microtubule (MTs) is a long protein filament that forms of a dynamic cytoskeletal within a morphological change. MTs have multiple functions in the cellular processes including a peculiar biophysical setting in the internal environment. MTs grow and shrink continually in the living cells qua the harmony between these processes is vital for normal cell function [1-5]. Microtubules are tubularpolymers (as its name points) and its diameter is about 24 min which the hetero dimers are assembled head to tail in a polar fashion (This polarity is reflected by the distinction between the socalled plus and minus ends of proto-filaments). The “building brick” from which they are formed called alpha and beta-tubulins that are proteins and occurs in solution as a dimer of two similar subunits [4,5]. Their assembly is in part determined by the concentration of free tubulins in the cytoplasm [3]. Although most of MTs combinations are largely deprived from the cytoplasmic influence, 2 nm2 lateral pores and 200 nm2 entrances at its ends are connected to cytoplasm [4, 5]. Recently, spherical particles have been found in the microtubules which the particles’ existence varied between cell types while the neuronal cells have the most particles [6-9]. In 1984, Burton exhibited the particles could be voided from the lumen quickly via reassembly or disassembly of intracellular microtubule [10]. Although identification of components inside of luminal has been difficult, during of the next 30 years observation of these particles in the microtubules lumen has culminated using vitreous cryo-electron microscopy [11]. These subunits polymerise end to end for formation protofilaments similar to a hollow tubes and their dynamic instability is controlled by numerous compounds. Proteins that destabilize microtubules have been identified recently (such as stathmin family proteins and Colchicine) [12-14]. These proteins increase microtubule turnover in cells, contributing to rapid reorganization of the microtubule cytoskeleton. Stathmin family was initially identified as a protein in response to extracellular signals, overexpressed in highly proliferative breast cancers and malignant ovarian cancers [15,16]. Stathmin is a cellular microtubule inhibitor, which forms a tight complex with two αβ-tubulin dimers, In the references [15,16] the structural information has shown how the stathmin protein family binds tubulin dimers and those studies suggest that phosphorylation occurs in a localized fashion, resulting in decreased microtubule destabilizing activity near microtubule polymer [17]. One of the important stathmin family proteins is RB3 which shares with other members the stathmin-like domain (SLD). Stathmin is a disordered protein, and their activities are downregulated by multiple phosphorylation. Stathmin is derived from the Greek word “stathmos” and it can also be translated as “terminal or stop”, which this translation loosely fits the microtubule destabilizing for the terminating or stopping microtubule growth [18]. Stathmin is a soluble, cytoplasmic protein which enforces an important function in regulating rapid microtubule remaking of the cytoskeleton in response to the cell’s requirements. At low concentrations of free tubulin in the cytoplasm, the growth rate at the microtubule ends is languid and results in an increased rate of disassembly (de-polymerization) [19]. The intracellular concentration of stathmin varies considerably among different cell types, ranging from0.005% up to 0.5% of the total cell protein [20], and in vertebrates, is expressed in cells with the potential to proliferate as well as in neurons [20,21].
Authors and Affiliations
Majid Monajjemi, Farnoush Naghsh, Afshar Alihosseini
Keywords
Related Articles
- EP ID EP576901
- DOI 10.26717/BJSTR.2017.01.000442
- Views 140
- Downloads 0
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