Phospho-TPPP (Ser18) Antibody - #AF8329

Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath. Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath. Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes. Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear. In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network. Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6. Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in increased acetylation of tubulin and increased cell motility. Plays a role in cell proliferation by regulating the G1/S-phase transition. Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2.

Phosphorylated by LIMK1 on serine residues; phosphorylation may alter the tubulin polymerization activity. Phosphorylation by LIMK2, but not LIMK1, regulates astral microtubule organization at early stage of mitosis. Phosphorylation by ROCK1 at Ser-32, Ser-107 and Ser-159 inhibits interaction with HDAC6, resulting in increased acetylation of tubulin, increased cell motility and entry into S-phase. Phosphorylation by CDK1 inhibits the microtubule polymerizing activity.

Degraded by the proteasome; zinc-binding inhibits degradation by the proteasome.

Postsynaptic Golgi apparatus. Cytoplasm>Cytoskeleton>Microtubule organizing center. Cytoplasm>Cytoskeleton. Nucleus. Cytoplasm>Cytoskeleton>Spindle.
Note: Specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, which shapes dendrite morphology by functioning as sites of acentrosomal microtubule nucleation (By similarity). Mainly localizes to the cytoskeleton (PubMed:18028908). Also found in the nucleus; however, nuclear localization is unclear and requires additional evidences (PubMed:18028908). Localizes to glial Lewy bodies in the brains of individuals with synucleinopathies (PubMed:15590652, PubMed:17027006). During mitosis, colocalizes with LIMK2 at the mitotic spindle (PubMed:22328514).

Widely expressed.

Homodimer. Binds tubulin; binding is inhibited by GTP. Interacts with MAPK1 (By similarity). Interacts with GAPDH; the interaction is direct (By similarity). Interacts with LIMK1 (via the PDZ domain); the interaction is direct. Interacts with LIMK2. Interacts with HDAC6; thereby inhibiting the tubulin deacetylase activity of HDAC6. Interacts with aggregated SNCA; may have a pro-aggregatory role in synucleinopathies. Interacts with DYNLL1.

Most of the protein is composed of disordered regions (PubMed:21316364). Zinc-binding induces structural rearrangement by promoting molten globule state formation (PubMed:21995432).

Belongs to the TPPP family.