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IQGAPs
are large scaffolding proteins that are intimately involved in controlling
cell motility, morphogenesis and adhesion. Most of our work so far
with these proteins has been directed at IQGAP1, and its role in coupling
growth factor stimulation of cells to assembly in the cell cortex
of branched actin filament networks. These networks function as the
engines for plasma membrane protrusion during cell migration, and
our results have indicated that IQGAP1 is required for their formation
in many cell types.
The histopathological hallmark of Alzheimer's disease is the presence in brain of extracellular deposits containing ß-amyloid peptide fibrils plus intraneuronal neurofibrillary tangles, which are filaments composed of the protein, tau. The goal of our work on AD is to decipher the metabolic link that connects ß-amyloid and tau to damage neurons. We have found that tau expression makes microtubules hypersensitive to pre-fibrillar forms of ß-amyloid, and suspect that tau-dependent, ß-amyloid-induced microtubule disassembly is a seminal event in AD pathogenesis at the cellular level.
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