Tubulin polymerization‐promoting protein (TPPP/p25) is critical for oligodendrocyte differentiation

Abstract

TPPP/p25, a recently identified tubulin polymerization promoting protein (TPPP), is expressed mainly in myelinating oligodendrocytes of the CNS. Here we show that TPPP/p25 is strongly upregulated during the differentiation of primary oligodendrocyte cells as well as the CG-4 cell line. The microRNA expression profile of CG-4 cells before and after induction of differentiation was established and revealed differential regulation of a limited subset of microRNAs. miR-206, a microRNA predicted to target TPPP/p25, was not detected in oligodendrocytes. Over-expression of miR-206 led to down-regulation of TPPP/p25 resulting in inhibition of differentiation. Transfection of siRNAs against TPPP/p25 also inhibited cell differentiation and promoted cell proliferation, providing evidence for an important role of TPPP/p25 during oligodendrogenesis. These results support an essential role for TPPP/p25 in oligodendrocyte differentiation likely via rearrangement of the microtubule system during the process elongation prior to the onset of myelination.

Challenging drug target for Parkinson's disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins

“…9). The specificity is further supported by the unique fact that the assembly of these two disordered hallmarks occurs exclusively at pathological conditions since in normal brain SYN and TPPP/p25 are expressed in neurons [57,58] and oligodendrocytes [9,59], respectively. Previously we showed that TPPP/p25, similarly to SYN, could be taken up by cells from the medium [35].…”

“…TPPP/p25 is a Microtubule Associated Protein; its expression is finely controlled in the human brain [7][8][9]. It is an intrinsically disordered protein (IDP) without a well-defined 3D structure, whose middle, highly flexible CORE region is straddled by the unstructured Nand C-termini [10].…”

“…It is an intrinsically disordered protein (IDP) without a well-defined 3D structure, whose middle, highly flexible CORE region is straddled by the unstructured Nand C-termini [10]. TPPP/p25 modulates the dynamics and stability of the microtubule system, where it is primarily engaged in the development of projections of oligodendrocytes that are responsible for the ensheathment of axons [7,9,11]. A couple of specific binding domains in the disordered TPPP/p25 have been identified both sequentially and experimentally such as a zinc finger motif, consensus GTP binding domain, phosphorylation sites, and the functional consequences of these sites have been established ( [12] and references therein).…”

On the tubulin polymerization promoting proteins of zebrafish

“…It is known that both TPPP1 and TPPP3 can be found in adult brains of various mammals. The exact localization of TPPP3 in brain is not known but TPPP1 can be found physiologically in oligodendroglia not in neurons [21][22][23]. Whilst TPPP1 seems to be brain-specific, TPPP3 has been found in other tissues as well [24][25][26].…”

Tubulin polymerization promoting protein (TPPP) ortholog from Suberites domuncula and comparative analysis of TPPP/p25 gene family

“…TPPP/p25 is being intensively studied due to its role in brain function and deregulation leading to synucleinopathies, a group of neurodegenerative disorders characterized by fibrillary aggregates of α-synuclein protein in the cytoplasm of selective populations of neurons and glia (Marti et al 2003;Orosz et al 2009). TPPP/p25 has also been recently shown to be critical for oligodendrocyte differentiation, where its downregulation inhibits differentiation and promotes cell proliferation (Lehotzky et al 2010).…”