PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility.

Integrin binding to matrix proteins such as fibronectin (FN) leads to formation of focal adhesion (FA) cellular contact sites that regulate migration. RhoA GTPases facilitate FA formation, yet FA-associated RhoA-specific guanine nucleotide exchange factors (GEFs) remain unknown. Here, we show that proline-rich kinase-2 (Pyk2) levels increase upon loss of focal adhesion kinase (FAK) in mouse embryonic fibroblasts (MEFs).

The complex relation between genotype and phenotype in motor neuron disease.

The success in mapping genetic loci and identifying mutant genes in familial neurodegenerative disease has outpaced our ability to understand the linkage between genotype and phenotype of disease. The results have led to a backlog of genetic information with limited clarification of underlying disease mechanisms. A major dilemma is how mutations in widely expressed proteins lead to degeneration or dysfunction of small subsets of neurons.

Coregulation of light neurofilament mRNA by poly(A)-binding protein and aldolase C: implications for neurodegeneration.

The multifunctional proteins aldolase C and poly (A)-binding protein (PABP) undergo competitive interactions in cells coexpressing aldolase C and NF-L. A specific in vivo interaction between aldolase C and NF-L mRNA had been localized to a 68 nt segment of the transcript spanning the translation termination signal. It is shown here that the poly (A)-binding protein (PABP) binds the body of the NF-L transcript and increases its levels of expression when an excess of PABP is transiently provided in trans.

HoxB2 binds mutant SOD1 and is altered in transgenic model of ALS.

Mutations in Cu/Zn superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis by a toxic gain of function; however, the precise mechanisms remain unclear. Here, we report the identification of HoxB2, a homeodomain-containing transcription factor, as a G93A mutant SOD1 interactive protein in a yeast two-hybrid screen. We show that HoxB2 co-precipitates and co-localizes with mutant SOD1 in neuronal cell lines, as well as in brain and spinal cord of G93A mutant SOD1 transgenic mice.

Aldolases a and C are ribonucleolytic components of a neuronal complex that regulates the stability of the light-neurofilament mRNA.

A 68 nucleotide segment of the light neurofilament (NF-L) mRNA, spanning the translation termination signal, participates in regulating the stability of the transcript in vivo. Aldolases A and C, but not B, interact specifically with this segment of the transcript in vitro. Aldolases A and C are glycolytic enzymes expressed in neural cells, and their mRNA binding activity represents a novel function of these isozymes.