Growth-associated protein-43 (GAP-43) is a major growth cone protein whose phosphorylation by PKC in response to extracellular guidance cues can regulate F-actin behavior. Here we show that 100% of homozygote GAP-43 (-/-) mice failed to form the anterior commissure (AC), hippocampal commissure (HC), and corpus callosum (CC) in vivo. Instead, although midline fusion was normal, selective fascicu...

It has been demonstrated that during neurogenesis in the mammalian brain, cell-cycle lengthening in neuronal progenitors may cause them to switch from proliferation to neuron-generating division. However, little is known about the cellular mechanisms involved in lengthening of the cell cycle. Growth-associated protein-43 (GAP-43) is a nervous system-specific protein whose expression in prolifer...

GAP-43 (growth-associated protein, 43 x 10(3) M(r)) is an essential, membrane-associated, neuronal phosphoprotein in vertebrates. The protein is abundantly produced in the growth cones of developing and regenerating neurons, and it is phosphorylated upon induction of long-term potentiation (LTP). Prior work has identified GAP-43-like proteins only in chordates. In this paper, a nervous system-s...

The neuronal ELAV-like RNA-binding protein HuD binds to a regulatory element in the 3'-untranslated region of the growth-associated protein-43 (GAP-43) mRNA. Here we report that overexpression of HuD protein in PC12 cells stabilizes the GAP-43 mRNA by delaying the onset of mRNA degradation and that this process depends on the size of the poly(A) tail. Using a polysome-based in vitro mRNA decay ...

Distributions of growth-associated protein-43 (GAP-43) in the periodontal ligament and dental pulp of adult rats were studied by light and electron microscopy. The mature periodontal ligament and dental pulp contained numerous GAP-43-positive neural elements, comprising periodontal Ruffini endings and thin nerve fibers, but expression patterns differed among the kinds of nerves. In the periodon...

We have shown previously that GAP-43 gene expression during neuronal differentiation is controlled by selective changes in mRNA stability. This process was found to depend on highly conserved sequences in the 3' untranslated region (3' UTR) of the mRNA. To map the sequences in the GAP-43 3' UTR that mediate this post-transcriptional event, we generated specific 3' UTR deletion mutants and chime...

Increasing evidence points to the importance of local protein synthesis for axonal growth and responses to axotomy, yet there is little insight into the functions of individual locally synthesized proteins. We recently showed that expression of a reporter mRNA with the axonally localizing β-actin mRNA 3'UTR competes with endogenous β-actin and GAP-43 mRNAs for binding to ZBP1 and axonal localiz...

Using transgenic mice, we have examined the expression pattern conferred by regions of genomic GAP-43 coupled to beta-galactosidase. We demonstrate that gene constructions that include the GAP-43 5'-flanking region along with sufficient sequences of the first intron drive beta-galactosidase (lacZ) expression to mimic in many regards the complex spatial and temporal pattern of endogenous GAP-43 ...

The neuronal growth-associated protein GAP-43 is expressed maximally during development and regeneration, and is enriched at the cytosolic surface of the growth cone membrane. GAP-43 can activate the GTP-binding protein G(o) which is also a major component of the growth cone membrane. These findings have led to the hypothesis that GAP-43 might modulate neurite outgrowth by altering G-protein ac...