LRP1-mediated Endocytosis and Transmission of Tau Antibody Sampler Kit#42521,Cell Signaling Technology (CST),42521

Tau is a heterogeneous microtubule-associated protein that promotes and stabilizes microtubule assembly, especially in axons. In addition to its normal function, intracellular neurofibrillary tangle protein aggregates, composed of hyperphosphorylated helical bundles of tau, are a major hallmark of neurodegenerative diseases like Alzheimer's disease (AD) (1). Moreover, disease progression is also measured by the progressive spread and deposition of the protein aggregates via intercellular transfer of tau (2). Although the intercellular mechanism of protein aggregate transfer is poorly understood, low density lipoprotein receptor related protein 1 (LRP1) was identified as a regulator of tau uptake and spread (3). LRP1 is a type I transmembrane receptor that mediates the endocytosis of various ligands, including apolipoproteins and tau. Interestingly, human apolipoprotein E (ApoE), which also binds to LRP1, is genetically linked to AD (4). LRP1-mediated protein uptake, in addition to tau, may play an important role in AD progression. In addition to LRP1, other low density lipoprotein receptor related proteins, including SORL1, are genetically linked to AD, suggesting a conserved cellular mechanism that converges on this family of proteins that contributes to AD etiology (5). Once tau binds to LRP1, receiving cells are likely to internalize and process tau via the endosomal pathway, completing cell-to-cell transmission. Rab5, Rab7, and Rab11, members of the Ras superfamily of small Rab GTPases, are likely to regulate endosomal processing of tau (6).ÂJohnson, G.V. and Stoothoff, W.H. (2004)J Cell Sci117, 5721-9.Braak, H. and Braak, E. (1991)Acta Neuropathol82, 239-59.Rauch, J.N. et al. (2020)Nature580, 381-385.Corder, E.H. et al. (1993)Science261, 921-3.Yin, R.H. et al. (2015)Mol Neurobiol51, 909-18.Zhang, X. et al. (2019)ACS Chem Neurosci10, 828-838.