Protein interacting with NIMA (never in mitosis A)-1 regulates axonal growth cone adhesion and spreading through myristoylated alanine-rich C kinase substrate isomerization.

Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine-rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation-dependent role in the modulation of axonal growth cone adhesion. The ratio of phospho-MARCKS (MARCKS-P) to total MARCKS controls adhesion modulation and spreading of the axonal growth cone.

Amyloid precursor protein is an autonomous growth cone adhesion molecule engaged in contact guidance.

Amyloid precursor protein (APP), a transmembrane glycoprotein, is well known for its involvement in the pathogenesis of Alzheimer disease of the aging brain, but its normal function is unclear. APP is a prominent component of the adult as well as the developing brain. It is enriched in axonal growth cones (GCs) and has been implicated in cell adhesion and motility.

Functional complexity of the axonal growth cone: a proteomic analysis.

The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level.

Group IVA phospholipase A₂ is necessary for growth cone repulsion and collapse.

The repellent semaphorin 3A (Sema3A) causes growth cone turning or collapse by triggering cytoskeletal rearrangements and detachment of adhesion sites. Growth cone detachment is dependent on eicosanoid activation of protein kinase C epsilon (PKCε), but the characterization of the phospholipase A(2) (PLA(2) ) that releases arachidonic acid (AA) for eicosanoid synthesis has remained elusive. Here, we show, in rat dorsal root ganglion (DRG) neurons, that Sema3A stimulates PLA(2) activity, that Sema3A-induced growth cone turning and collapse are dependent on the release of AA, and that the primary PLA(2) involved is the group IV α isoform (GIVA).

Dynamic adhesions and MARCKS in melanoma cells.

Cell motility necessitates the rapid formation and disassembly of cell adhesions. We have studied adhesions in a highly motile melanoma cell line using various biochemical approaches and microscopic techniques to image close adhesions. We report that WM-1617 melanoma cells contain at least two types of close adhesion: classic focal adhesions and more extensive, irregularly shaped adhesions that tend to occur along lamellipodial edges.