The tau protein is a microtubule associated protein found mostly in neuronal cells where it regulates the stability of axonal microtubules as well as kinesin-dependent transport. Tau is relevant in the study of various neurological disorders as abnormal post translational modifications can alter its structure and lead to protein aggregates. Tau is present on microtubules in neuronal cells and is also associated with the plasma membrane. Nuclear structures are also recognized by various tau antibodies indicating a potential nuclear function as well (1). Tau is alternatively spliced into six different isoforms that are expressed differentially during brain development (1). Tau interacts with microtubules through 3-4 microtubule binding domains, depending on the isoform, and this association can be regulated by various kinases and phosphatases (2). While tau phosphorylation is required for binding to and stabilizing microtubules, hyperphosphorylated tau forms aggregates or neurofibrillary tangles that can inhibit the assembly and disrupt the organization of microtubules. Improper folding of tau leads to the neurofibrillary tangles that are seen in neurons affected by Alzheimer’s disease. Disease-specific tau antibodies that recognize hyperphosphorylated or misfolded tau protein have served as an important diagnostic tool as the abundance of neurofibrillary tangles correlates well with disease progression (3). Additionally, monoclonal tau antibodies for specific phospho-isoforms have been used in conjunction with mass spectrometry to characterize the numerous phosphorylation sites and their roles in tau protein folding and tau-associated pathologies (2). While the tau protein has yet to be crystalized, NMR spectroscopy and studies with tau antibodies have provided information regarding domain structures and the organization of epitopes with respect to one another (3). Given the difficulty of biochemical analysis of the tau protein and its higher-order structures, alternative techniques such as electron microscopy, NMR, mutational analyses, and assays with panels of tau antibodies have been essential for understanding the effects of post translational modifications on tau structure in health and disease. Continued investigation of tau structure and function will help understand its biological functions and our understanding of its role in various neuronal disorders.
Novus Biologicals offers Tau reagents for your research needs including:
PMIDs
