Comparative distribution of myristoylated alanine-rich C kinase substrate (MARCKS) and F1/GAP-43 gene expression in the adult rat brain

Abstract

Myristoylated alanine-rich C-kinase substrate (MARCKS) and F1/GAP-43 (B-50/neuromodulin) are both major specific substrates for protein kinase C (PKC) and appear to play an important role in the regulation of neuroplastic events during development and in the adult brain. Since PKC isozymes are differentially expressed in brain and the expression of F1/GAP-43 and MARCKS are differentially regulated by PKC through posttranslational mechanisms, the present study examined the relative distribution of both mRNAs in the adult brain by using in situ hybridization histochemistry. MARCKS hybridization was most pronounced in the olfactory bulb, piriform cortex (layer II), medial habenular nucleus, subregions of the amygdala, specific hypothalamic nuclei, hippocampal granule cells, neocortex, and cerebellar cortex, intermediate in the superior colliculus, hippocampal CA1, and certain brainstem nuclei including the locus coeruleus, and low-absent in regions of the caudate-putamen, geniculate, thalamic nuclei, lateral habenular nucleus, and hippocampal CA3 pyramidal and hilar neurons. Consistent with previous reports, prominent F1/GAP-43 hybridization was observed in neocortex, medial geniculate, piriform cortex (layer II), substantia nigra pars compacta, hippocampal CA3 pyramidal cells, thalamic and hypothalamic nuclei, lateral habenular nucleus, locus coeruleus, raphe nuclei, and cerebellar granule cells, intermediate in regions of the thalamus, hypothalamus, and amygdala, and low-absent in regions of the olfactory bulb, caudate-putamen, medial habenular nucleus, hippocampal granule cells, and superior colliculus. Overall, F1/GAP-43 was highly expressed in a greater number of regions compared to MARCKS and, in a number of regions, including the hippocampus, habenular complex, ventral tegmentum, geniculate, and certain brain stem nuclei, a striking inverse pattern of expression was observed. These results indicate that MARCKS gene expression, like that of F1/GAP-43, remains elevated in select regions of the adult rat brain which are associated with a high degree of retained plasticity. The potential role of PKC in the regulation of MARCKS and F1/GAP-43 gene expression in brain is assessed.

Alterations of the myristoylated, alanine-rich C kinase substrate (MARCKS) in prefrontal cortex in schizophrenia

“…MARCKS is central to these neurotransmitter pathways and is a potential molecular mechanism underlying synaptic plasticity, given the mediatory role of MARCKS in translating Ca 2+ dependent kinase activity into dynamic cytoskeletal restructuring (Leenders and Sheng, 2005; Ramakers et al, 1999). Localized to axon terminals, dendritic spines and glial processes (Ouimet et al, 1990; Ramakers et al, 1999), MARCKS is highly expressed during development, and remains high in adulthood in neuronal populations with high degrees of neuroplasticity; these include the hippocampus, amygdala and multiple cortical regions (McNamara et al, 2005; McNamara and Lenox, 1997; Ouimet et al, 1990; Ramakers et al, 1999). Decreased MARCKS expression is consistent with changes in Ca 2+ induced vesicular transport and synaptic vesicle cycling, via MARCKS interactions with PKC, PI(4,5)P2, and cellular membranes (Horn, 1998; Rose et al, 2001; Sasaki, 2003; Walaas and Sefland, 2000; Yang et al, 2002).…”

Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons

“…It is also relevant to the remodeling of synaptic connections in the intact nervous system. Although GAP-43, CAP-23 and other growth-associated proteins are generally suppressed in the adult nervous system, each of these GAPs persists in a distinct subpopulation of adult neurons [36][37][38][39][40] . Our results indicate that the differential expression of individual GAPs provides a mechanism to modulate local remodeling of axon terminals without triggering long-distance growth of primary axons.…”

Impaired Sprouting and Axonal Atrophy in Cerebellar Climbing Fibres following In Vivo Silencing of the Growth-Associated Protein GAP-43

“…The expression of GAP-43 is high in the brain during development and it declines in most neurons when mature synapses are formed. However in some brain regions a high expression of GAP-43 is maintained throughout life [7], [8] and it is suggested to play an important role in synaptic plasticity and synaptic vesicle release during adulthood [4]–[6], [9]. This is confirmed by studies performed on mice lacking one or both copies of Gap-43 gene or expressing a point-mutated form, revealing alterations in well established learning and memory paradigms [10]–[14].…”

“…To this aim the cerebellar cortex provides an excellent model due to its high degree of structural plasticity [22]–[30]. The IO is among the regions retaining a high expression of GAP-43 throughout life [7], [8], [31]. Additionally, CFs, which are the terminal arbors of the axon of olivary neurons, innervate the dendrites of the PCs in a one-to-one relationship, displaying a well characterised three-dimensional organization [32], [33].…”