Spastin Antibody #79310

Spastin (SPG4) is a member of the ATPases associated with multiple cellular activities (AAA) protein family that contains a microtubule interacting and organelle transport (MIT) domain. There are four spastin isoforms, which are imported into the nucleus. One of the isoforms contains two nuclear export signals that efficiently drive export to the cytoplasm (1,2). Spastin is involved in severing polyglutamylated microtubules and regulates microtubule abundance and mobility (3). Spastin promotes endosomal tubule fission through interaction of the endoplasmic reticulum (ER)-localized spastin isoform, M1-spastin, and the endosomal IST1 protein at ER-endosome contacts. Rescue of endosomal tubulation phenotypes requires spastin's microtubule-severing ATPase capacity and its ability to bind the endosomal proteins IST1 and CHMP1B (4). Spastin regulates microtubule stability to modulate synaptic structure and function, and it is essential for synaptic formation and axonal growth in developing neurons (1,5). Spastin is linked to several diseases, including Hereditary Spastic Paraplegia (HSP), which affects upper motor neurons within the tubular ER membrane in corticospinal neurons (6). Some data suggest that spastin interacts with Lewy bodies and liquid droplets in Parkinson's disease (7). Tau missorting in Alzheimer's disease is strongly related to the formation of pathological tau aggregates and induces a mislocalization of tubulin-tyrosine-ligase-like protein 6 (TTLL6), leading to TTLL6-induced polyglutamylation of microtubules that trigger spastin-mediated severing of dendritic microtubules (8).