MAP1B enhances microtubule assembly rates and axon extension rates in developing neurons.

The microtubule-associated protein MAP1B is known to have important roles in neuronal development, particularly during neuronal migration and axonogenesis, but its precise molecular actions are unknown. We used RNA interference silencing of protein expression to specifically knock down MAP1B in cultured embryonic rat cortical neurons. Reduction of MAP1B in these neurons is associated with several abnormal morphological phenotypes including the production of more highly branched and slower growing axons than normal.

β1 integrins regulate fibroblast chemotaxis through control of N-WASP stability.

Chemotactic migration of fibroblasts towards growth factors, such as during development and wound healing, requires precise spatial coordination of receptor signalling. However, the mechanisms regulating this remain poorly understood. Here, we demonstrate that β1 integrins are required both for fibroblast chemotaxis towards platelet-derived growth factor (PDGF) and growth factor-induced dorsal ruffling.

Nonprimed and DYRK1A-primed GSK3 beta-phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons.

MAP1B is a developmentally regulated microtubule-associated phosphoprotein that regulates microtubule dynamics in growing axons and growth cones. We used mass spectrometry to map 28 phosphorylation sites on MAP1B, and selected for further study a putative primed GSK3 beta site and compared it with two nonprimed GSK3 beta sites that we had previously characterised. We raised a panel of phosphospecific antibodies to these sites on MAP1B and used it to assess the distribution of phosphorylated MAP1B in the developing nervous system.

The microtubule-associated protein tau is also phosphorylated on tyrosine.

Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease (AD), where it is hyperphosphorylated on serine and threonine residues. It is hypothesized that this hyperphosphorylation contributes to neurodegeneration through the destabilization of microtubules. There is now evidence that phosphorylation of tau can also occur on tyrosine residues.

The microtubule-associated protein tau is phosphorylated by Syk.

Aberrant phosphorylation of tau protein on serine and threonine residues has been shown to be critical in neurodegenerative disorders called tauopathies. An increasing amount of data suggest that tyrosine phosphorylation of tau might play an equally important role in pathology, with at least three putative tyrosine kinases of tau identified to date. It was recently shown that the tyrosine kinase Syk could efficiently phosphorylate alpha-synuclein, the aggregated protein found in Parkinson's disease and other synucleinopathies.

Tyrosine 394 is phosphorylated in Alzheimer's paired helical filament tau and in fetal tau with c-Abl as the candidate tyrosine kinase.

Tau is a major microtubule-associated protein of axons and is also the principal component of the paired helical filaments (PHFs) that comprise the neurofibrillary tangles found in Alzheimer's disease and other tauopathies. Besides phosphorylation of tau on serine and threonine residues in both normal tau and tau from neurofibrillary tangles, Tyr-18 was reported to be a site of phosphorylation by the Src-family kinase Fyn. We examined whether tyrosine residues other than Tyr-18 are phosphorylated in tau and whether other tyrosine kinases might phosphorylate tau.