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.

SorLA is a sorting protein in neurons with relevance to Alzheimer's disease (AD). It shares roles with the caveolins, markers of the lipid 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 (cav1), a caveolar microdomain marker. RT‐PCR and immunoblots demonstrated sorLA expression in rat cells: C6 glioma, primary cultures astrocytes (PCRA) and 1321N1 human astrocytoma cells. Differentiation of C6 cells to an astrocyte phenotype (C6 diff) led to a significant decrease in sorLA's mRNA and protein expression. Sucrose density gradient revealed cofractionation of sorLA with cav1 in light density membrane raft fractions of undifferentiated C6, C6 diff and 1321N1 cells. Immunofluorescences analysis of C6 and PCRA revealed a cellular distribution akin to sorLA's staining pattern in neurons. In C6 and PCRA cells a significant percent of sorLA colocalized with cav1, mostly in perinuclear compartments, cytoplasmic vesicles and plasmalemma. These findings establish that sorLA is expressed in glia and is a membrane raft protein involved with cav1 in glial intracellular membrane microdomains trafficking. This study supports a role for glia and its caveolar membrane raft microdomains to the sorting functions of sorLA in the neurodegenerative cascade of AD, unveiling new venues for disease treatment.