Question

Describe the large family of microtubule-associated proteins (MAPs) including specific members and their characteristics (structure, function, homology, etc) and how the Tau proteins fit into this family.

Answer 1

STRUCTURE OF MICROTUBULE ASSOCIATED PROTEINS

Microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton. Microtubule- associated proteins of the MAP2/Tau family include the vertebrate proteins MAP2,MAP4 and Tau and homologs in other animals.All three vertebrate members of the family have alternative splice forms . All isoforms share a conserved carboxy-terminal domain containing microtubule-binding repeats and an aminoterminal projection domain of varying size. MAP2 and Tau are found in neurons,whereas MAP4 is present in many other tissues but is generally absent from neurons.Members of the family best known for their microtubule - stabilizing activity and for proposed roles regulating microtubule networks in the axons and dendrites of neurons.Contrary to this simple ,traditional view, accumulating evidence suggests a much broader range of functions such as binding to filamentous actin , recruitment of signaling proteins, and regulation of microtubule -mediated transport.Tau is also implicated in Alzheimer's disease and other dementias.Various upstream kinases and interacting proteins have been identified that regulate the microtubule stabilizing activity of MAP2/Tau family proteins.  

FUNCTIONS OF MICROTUBULE ASSOCIATED PROTEINS

MAPs bind to the tubulin subunits that make up microtubules to regulate their stability. A large variety of MAPs have been identified in many different cell types,and they have been found to carry out a wide range of functions.These include both stabilizing and destabilizing microtubules ,guiding microtubules towards specific cellular locations,cross-linking microtubules and mediating the interactions of microtubules with other proteins in the cell.Within the cell MAPs bind directly to the tubulin dimers of microtubules .This binding can occur with either polymerizes or depolymerized tubulin, and in most cases leads to the stabilization of microtubule structure,further encouraging polymerization.

HOMOLOGY OF MAPs

Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology.A complementary DNA encoding the D 100 poly-peptide of rat brain dynamin producing microtubule activated nucleotide triphosphatase has been cloned and sequenced.The predicted amino acid sequence includes a guanine nucleotide-binding domain that is homologous with those of a family of antiviral factors , inducible by interferon and known as MX proteins and with the product of the essential yeast vacuolar protein sorting gene VPS1.These relationships imply the existence of a new family of GTPases with physiological roles that may include microtubule based motility and protein sorting.

Microtubule associated proteins are essential for the formation of cytoskeletal architecture. Transfection of tau suppressed organelle movement almost completely in this cell type, hence interaction of axonal MAPs with microtubules interferes with organelle transports.Tau proteins stabilize microtubules.They are abundant in neurons of the central nervous system and are less common elsewhere,but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.