Expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion neurons: Caveolin-2 is up-regulated in response to cell injury

Abstract

Caveolae are cholesterol͞sphingolipid-rich microdomains of the plasma membrane that have been implicated in signal transduction and vesicular trafficking. Caveolins are a family of caveolae-associated integral membrane proteins. Caveolin-1 and -2 show the widest range of expression, whereas caveolin-3 expression is restricted to muscle cell types. It has been previously reported that little or no caveolin mRNA species are detectable in the brain by Northern blot analyses or in neuroblastoma cell lines. However, it remains unknown whether caveolins are expressed within neuronal cells. Here we demonstrate the expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion (DRG) neurons by using mono-specific antibody probes. In PC12 cells, caveolin-1 expression is up-regulated on day 4 of nerve growth factor (NGF) treatment, whereas caveolin-2 expression is transiently up-regulated early in the differentiation program and then rapidly down-regulated. Interestingly, caveolin-2 is up-regulated in response to the mechanical injury of differentiated PC12 cells; up-regulation of caveolin-2 under these conditions is strictly dependent on continued treatment with NGF. Robust expression of caveolin-1 and -2 is also observed along the entire cell surface of DRG neurons, including high levels on growth cones. These findings demonstrate that neuronal cells express caveolins.

Caveolin proteins and estrogen signaling in the brain

“…Indeed, caveolar-like microdomains (CLMs) were termed as the neuronal counterpart to non-neuronal caveolae. More recently, however, various reports have demonstrated the expression off all three caveolin isoforms in neurons [29,30,[83][84][85][86]. Data described below is consistent with reports from non-neuronal tissue and the initial descriptions in Dominique Toran-Allerand's review that caveolin proteins play an essential role in brain membrane estrogen receptor function.…”

“…There are three known caveolin proteins, caveolin 1 (CAV1, with splice variants α and β), caveolin 2 (CAV2), and caveolin 3 (CAV3) [26][27][28]. CAV1 and CAV2 have overlapping expression patterns in a variety of cell types including, neurons and glia [29,30], endothelial [31], and epithelial cells [32]. Disruption of CAV2 expression does not affect caveolae formation in vivo [33], inasmuch it is hypothesized that CAV2 only forms caveolae as hetero-oligomers with CAV1, and not in isolation [34].…”

Porin Is Present in the Plasma Membrane Where It Is Concentrated in Caveolae and Caveolae-related Domains

“…Although caveolin was detected in caveolae and the phosphate carrier in mitochondria, porin was present in both fractions. The presence of caveolae in nervous tissue has been recently established (24,25). Furthermore a procedure for the purification of caveolae using Na 2 CO 3 2 V. De Pinto, unpublished observations.…”

Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling

“…Dynamic changes in its expression clearly implicate caveolin-1 in regulation of cell growth. Caveolin-1 is upregulated upon induction of differentiation in various cell types (Scherer et al, 1994;Galbiati et al, 1998b;Li et al, 2001). Conversely, caveolin-1 is downregulated upon oncogenic transformation (Koleske et al, 1995;Engelman et al, 1998a).…”