Glial cells prevail in number and in diversity of cellular phenotypes in the nervous system. They have also gained prominence due to their multiple physiological and pathophysiological roles. Our current knowledge of the asymmetry and heterogeneity of the plasma membrane demands an in depth analysis of the diverse array of membrane microdomains postulated to exist in the context of glial cells. This review focuses and analyzes the studies reported to date on the detection of caveolae membrane rafts and the caveolin family members in glial cell model systems, the conditions leading to changes in their level of expression, and their functional and clinical significance. Outstanding in this work emerge the ubiquitous expression of caveolins, including the typically regarded 'muscle-specific' cav3, in diverse glial cell model systems, their participation in reactive astrogliosis, cancer, and their key relevance to calcium signaling. The knowledge obtained to date demands incorporation of the caveolins and caveolae membrane rafts in our current models on the role of glial cells in heath and neurological disease. The relative abundance of glia parallels their increasingly evident roles in nervous system physiology and pathophysiology. The diversity in functional roles of glia relates to the main different types of glia: the myelinating oligodendrocytes (OL) and Schwann cells (SC), the fibrous (white matter) and protoplasmic (gray matter) astrocytes, perivascular astrocytes, radial glia, and the mesodermally derived microglia, which are key players in nervous system inflammatory responses. Astrocytes are known to participate in nutrient transport, ionic homeostasis, mechanical support, synaptic plasticity, and blood-brain barrier integrity (Hansson and Ronnback 2003). Astrocyte activation, known as reactive astrogliosis, ensues during pathophysiological processes such as injury, trauma, ischemia, stroke, neurodegenerative disorders, aging, and brain tumor formation. Depending on the type of insult, extent and time point astrocytes may exert opposite cytoprotective or cytotoxic actions (Fellin and Carmignoto 2004).Paramount to the understanding of the functional roles of glia in the nervous system is the recognition of plasmalemma lipid heterogeneity, asymmetry, and distinct membrane microdomains. This review focuses on the caveolae (CAV) membrane microdomain, and its constituent or marker proteins the caveolins. The present review addresses the studies performed in glial cell model systems in the following areas: ultrastructural analysis of CAV, detection of caveolin1 (cav1) and 2, the expression of the 'muscleAddress correspondence and reprint requests to Dr Walter I. Silva, Department of Physiology, School of Medicine, University of Puerto Rico, PO Box 365067, San Juan 00936-5067, Puerto Rico. E-mail: wsilva@rcm.upr.edu 1 Membrane rafts are small (10-200 nm), heterogeneous, highly dynamic, and sterol-and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabi...
SorLA is an established sorting and trafficking protein in neurons with demonstrated relevance to Alzheimer’s disease (AD). It shares these roles with the caveolins, markers of membrane rafts microdomains. To further our knowledge on sorLA’s expression and traffic, we studied sorLA expression in various cultured glia and its relation to caveolin-1 (cav-1), a caveolar microdomain marker. RT-PCR and immunoblots demonstrated sorLA expression in rat C6 glioma, primary cultures of rat astrocytes (PCRA), and human astrocytoma 1321N1 cells. PCRA were determined to express the highest levels of sorLA’s message. Induction of differentiation of C6 cells into an astrocyte-like phenotype led to a significant decrease in sorLA’s mRNA and protein expression. A set of complementary experimental approaches establish that sorLA and cav-1 directly or indirectly interact in glia: (1) co-fractionation in light-density membrane raft fractions of rat C6 glioma, PCRA, and human 1321N1 astrocytoma cells; (2) a subcellular co-localization distribution pattern in vesicular perinuclear compartments seen via confocal imaging in C6 and PCRA; (3) additional confocal analysis in C6 cells suggesting that the perinuclear compartments correspond to their co-localization in early endosomes and the trans-Golgi; and; (4) co-immunoprecipitation data strongly supporting their direct or indirect physical interaction. These findings further establish that sorLA is expressed in glia and that it shares its subcellular distribution pattern with cav-1. A direct or indirect cav-1/sorLA interaction could modify the trafficking and sorting functions of sorLA in glia and its proposed neuroprotective role in AD.
It has been suggested that drug tolerance represents a form of learning and memory, but this has not been experimentally established at the molecular level. We show that a component of alcohol molecular tolerance (channel internalization) from rat hippocampal neurons requires protein synthesis, in common with other forms of learning and memory. We identify -catenin as a primary necessary protein.Alcohol increases -catenin, and blocking accumulation of -catenin blocks alcohol-induced internalization in these neurons. In transfected HEK293 cells, suppression of Wnt/-catenin signaling blocks ethanol-induced internalization. Conversely, activation of Wnt/-catenin reduces BK current density. A point mutation in a putative glycogen synthase kinase phosophorylation site within the S10 region of BK blocks internalization, suggesting that Wnt/-catenin directly regulates alcohol-induced BK internalization via glycogen synthase kinase phosphorylation. These findings establish de novo protein synthesis and Wnt/-catenin signaling as critical in mediating a persistent form of BK molecular alcohol tolerance establishing a commonality with other forms of long-term plasticity.
Yield of taniers on a Corozal clay (Ultisol) decreased with increasing soil acidity from 16.3 t/ha at pH 5.0 with 12% saturation of the CEC with Al, to 4.2 t/ha at pH 4.2 and 70% Al saturation. Similar results were obtained on Corozal clay subsoil. Much lower yields were produced on Coto clay (Oxisol). These yields were lowered only at the highest acidity level, pH 4.5, and 34% Al saturation of the soil CEC. Foliar composition of the taniers was not affected by soil acidity, except that the Ca content was appreciably less at the highest level of acidity on the Corozal soil and subsoil. For all soils combined, pH and percent Al saturation of the soil CEC correlated very closely with yields. Overall yields were close to maximum when the soil had a pH of 5.2 and no exchangeable Al.
with >70% of the labeling in the b2 subunit. [ 3 H]chlorpromazine subunit labeling was inhibited (~40%) by the non-competitive antagonist PCP (Fig 1). When HPLC-purified EndoLys-C digests of [ 3 H]chlorpromazine-labeled b2 subunit was sequenced, a PCP-inhibitable 3 H release at cycle 6 was evident, consistent with labeling of b2Ser246 (M2-6), the position photolabeled by [ 3 H]chlorpromazine in the Torpedo nAChR ion channel. Sequence analyses of HPLC-purified EndoLys-C/V8 protease digests of a4 and b2 subunits photolabeled by [ 3 H]TDBzl-etomidate indicated the presence of multiple sites of 3 H incorporation. Studies are in progress to identify amino acids labeled by [ 3 H]TDBzl-Etomidate and [ 3 H]chlorpromazine.
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