Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the roles of various microtubule-associated proteins (MAPs) in the development of axons and dendrites, we have expressed individual neuronal MAPs in normally rounded Sf9 host cells. We previously reported that expression of tau protein in these cells results in the elaboration of long processes containing dense bundles of microtubules (MTs). These bundles generally terminate in the hillock region of the cell body, and almost all of the MTs within the bundles are oriented with their plus ends distal to the cell body. Here we report the expression of a construct that approximates the MAP2C sequence and also induces the elaboration of processes with dense bundles of predominantly plus-end-distal MTs. Whereas tau generally results in a single process, there is a significantly greater tendency for the MAP2C-like construct to induce multiple processes. In contrast to the tau processes, the MT bundle in these processes extends far into the cell body. This latter observation suggests that MAP2C and tau have different effects on MT assembly and/or transport events in the cell. Although both of these MAPs can organize MTs that are competent to participate in process formation, the detailed organization of MTs induced by each of the two constructs is distinctive, and these differences may be relevant to axonal and dendritic differentiation.
 ...
PMID:Process formation in Sf9 cells induced by the expression of a microtubule-associated protein 2C-like construct. 832 2

Axonal microtubules have two essential roles: providing the track for organelle transport and forming the cytoskeletal framework to maintain axonal morphology. Microtubule-associated proteins (MAPs) are essential for the formation of cytoskeletal architecture. However, they may have additional roles on the regulation of organelle transport by their interaction with motor proteins on the microtubules. We first examined the effects of axonal MAPs on the organelle movement along microtubules in a heterologous system using COS fibroblasts, which express no axonal MAPs, such as tau or MAP2C. Transfection of tau or MAP2C gene suppressed organelle movement almost completely in this cell type, hence interaction of axonal MAPs with microtubules interferes with organelle transports. It is known that the phosphorylation of MAPs reduces their interaction with microtubules. In this sense, phosphorylation of MAPs can be a good candidate for the molecular switch to regulate the organelle transport. As a second set of experiments, we investigated the effects of modulating cAMP dependent protein kinase pathway on organelle transports in primary sensory neurons, where high-molecular-weight tau protein is the major MAP. We found that the application of dibutyryl cAMP enhanced transports of large organelles in the axon. Furthermore, this drug treatment phosphorylated endogenous tau protein and thus reduced the affinity of tau to microtubules. These results indicate that axonal MAPs can work as a phosphorylation-dependent regulator of organelle transport. Local activation of protein kinase pathways in the axon might play an important role on the segregation of microtubules serving for either organelle transport or cytoskeletal architecture.
 ...
PMID:Microtubule-associated proteins regulate microtubule function as the track for intracellular membrane organelle transports. 911 34