A potential role for calcium / calmodulin-dependent protein kinase-related peptide in neuronal apoptosis: in vivo and in vitro evidence

Publication Type:

Journal Article

Source:

Eur J Neurosci, Volume 26, Number 12, p.3411-3420 (2007)

ISBN:

1460-9568 (Electronic)09

DOI Name (links to online publication)

10.1111/j.1460-9568.2007.05956.x

Keywords:

Adrenalectomy; Animals; Apoptosis/*physiology; Apoptosis Regulatory Proteins/*physiology; COS Cells; Cell Line; Tumor; Cercopithecus aethiops; Dentate Gyrus/cytology/*physiology; Drug Interactions; GRB2 Adaptor Protein/pharmacology; Male; Microinjections;

Abstract:

Previously, we have established that a product of the doublecortin-like kinase (DCLK) gene, DCLK-short, is cleaved by caspases during serum deprivation. Subsequently, the N-terminal cleavage product of DCLK-short facilitates apoptosis in the neuroblastoma cell line NG108. As this N-terminal cleavage product is highly homologous to calcium/calmodulin-dependent protein kinase-related peptide (CARP), another DCLK gene splice variant, we aimed to determine the possible apoptotic properties of CARP in vivo and in vitro. We report highly specific CARP expression in apoptotic granule cells in the rat dentate gyrus after adrenalectomy relative to healthy granule cells. CARP is significantly upregulated in the suprapyramidal blade of the dentate gyrus, with varying levels of upregulation, depending on the extent of adrenalectomy-induced apoptosis. Similar to the caspase-cleaved N-terminus of DCLK-short, CARP overexpression itself facilitated apoptosis in serum-deprived NG108 cells. Furthermore, CARP facilitated polymerization of tubulin in vitro and was capable of interacting with growth factor receptor-bound protein 2, an intracellular protein involved in vesicle trafficking. Together, our data demonstrate a facilitating role for CARP in the apoptotic process in granule cell populations sensitive to adrenalectomy, and suggest that this proapoptotic effect is mediated by increasing the stability of the microtubule cytoskeleton.

18/01/2013