Glycolipid‐Enriched Caveolae and Caveolae‐Like Domains in the Nervous System

Masserini, Massimo; Palestini, Paola; Pitto, Marina

doi:10.1046/j.1471-4159.1999.0730001.x

Cited by 104 publications

(75 citation statements)

References 120 publications

(206 reference statements)

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“…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.…”

Section: Caveolin Proteins and Estrogen Receptorssupporting

confidence: 87%

Caveolin proteins and estrogen signaling in the brain

Luoma

Boulware

Mermelstein

2008

Molecular and Cellular Endocrinology

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Best described outside the nervous system, caveolins are structural proteins that form caveolae, functional microdomains at the plasma membrane that cluster related signaling molecules. Caveolin associated proteins include G protein coupled receptors and G proteins, receptor tyrosine kinases, as well as protein kinases, ion channels and various other signaling enzymes. Not surprisingly, a wide array of biological disorders are thought to be rooted in caveolin dysfunction. In addition, caveolins also traffic and cluster estrogen receptors to caveolae. Interactions between the estrogen receptors ERα and ERβ with caveolins appear critical in many non-neuronal cell types, e.g. disruption of normal function may underlie many forms of breast cancer. Recent findings suggest caveolins may also play an essential role in membrane estrogen receptor function in the nervous system. Not only are they expressed in neurons and glia, but different caveolin isoforms also appear necessary to generate distinct functional signaling complexes. With membrane estrogen receptors responsible for the efficient activation of a multitude of intracellular signaling pathways, which in turn influence a wide variety of nervous system functions, caveolin proteins are poised to act as the central coordinators of these processes.

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Section: Caveolin Proteins and Estrogen Receptorssupporting

confidence: 87%

Caveolin proteins and estrogen signaling in the brain

Luoma

Boulware

Mermelstein

2008

Molecular and Cellular Endocrinology

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“…This could lead to dramatic changes in the pattern of proteins that PKD can phosphorylate in a nonnatural localization, explaining the increase in Kidins220-Ser 919 phosphorylation and indicating that altering raft structure may significantly affect PKD functions. These results also suggest that PKD activity, signaling, and function might be affected by the distinct lipid composition of membranes in different cell types or the alteration of membrane lipids either by the clinical use of lipid-lowering drugs or associated to several diseases (80).…”

Section: Treatment Increases Pkd-ser 748 and Tyrosine Phosphorylmentioning

confidence: 81%

Lipid Raft Disruption Triggers Protein Kinase C and Src-dependent Protein Kinase D Activation and Kidins220 Phosphorylation in Neuronal Cells

Cabrera-Poch¹,

Sánchez‐Ruiloba²,

Rodríguez-Martínez³

et al. 2004

Journal of Biological Chemistry

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Kidins220 (kinase D-interacting substrate of 220 kDa) is a novel neurospecific protein recently cloned as the first substrate for the Ser/Thr kinase protein kinase D (PKD). Herein we report that Kidins220 is constitutively associated to lipid rafts in PC12 cells, rat primary cortical neurons, and brain synaptosomes. Immunocytochemistry and confocal microscopy together with sucrose gradient fractionation show co-localization of Kidins220 and lipid raft-associated proteins. In addition, cholesterol depletion of cell membranes with methyl-␤-cyclodextrin dramatically alters Kidins220 localization and detergent solubility. By studying the putative involvement of lipid rafts in PKD activation and signaling we have found that active PKD partitions in lipid raft fractions after sucrose gradient centrifugation and that green fluorescent protein-PKD translocates to lipid raft microdomains at the plasma membrane after phorbol ester treatment. Strikingly, lipid rafts disruption by methyl-␤-cyclodextrin delays green fluorescent protein-PKD translocation, as determined by live cell confocal microscopy, and activates PKD, increasing Kidins220 phosphorylation on Ser 919 by a mechanism involving PKC⑀ and the small soluble tyrosine kinase Src. Collectively, these results reveal the importance of lipid rafts on PKD activation, translocation, and downstream signaling to its substrate Kidins220. Kidins220 (kinase D-interacting substrate of 220 kDa) 1 (1), also known as ankyrin repeat-rich membrane spanning or ARMS (2), is a novel integral membrane protein mainly expressed in brain, encoded by a single gene in Drosophila melanogaster, Caenorhabditis elegans, and mammals. Its primary amino acid sequence contains several structural and functional domains and diverse motifs that may link this protein to membranes, cytoskeleton, and different signaling pathways. The N terminus bears 11 ankyrin repeats that are likely to be involved in protein-protein interactions specially with the cytoskeleton (3). Downstream, the sequence presents four transmembrane domains and a proline-rich region that may serve as a binding site for adaptor modules like SH3 domains. Kidins220 C-terminal half is very abundant in phosphorylatable residues, serine, threonine, and tyrosine, that could constitute docking sites for Ser/Thr binding domain-containing proteins or phosphotyrosine binding modules such as SH2 domains. It also bears a sterile-␣ motif or SAM domain (4) and a potential PSD95/SAP90, DGL/ZO-1 (PDZ) binding motif at the very C terminus (5), both candidates for protein-protein interactions.Kidins220 was cloned as the first physiological substrate for protein kinase D (PKD) (1). This kinase, also known as PKD1 or protein kinase C (PKC) (6, 7), belongs to a novel family of diacylglycerol (DAG)-stimulated Ser/Thr kinases distantly related to the PKC family, characterized by unique enzymatic properties and domain architecture (for a recent review, see Refs. 8 and 9). PKD has multiple domains, including two cysteine-rich repeats that constitute a C1 domain...

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“…The structure and function of caveolae and lipid rafts in the nervous system is beginning to be elucidated (Maekawa et al, 2003;Masserini et al, 1999;Tsui-Pierchala et al, 2002) and these structures may become important in defining neurological and psychiatric disease. Data in this report clearly demonstrate that Gsa raft localization is altered by chronic antidepressant treatment, and that this may be due to an alteration of the membrane-associated microtubule cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Chronic Antidepressant Treatment Prevents Accumulation of Gsα in Cholesterol-Rich, Cytoskeletal-Associated, Plasma Membrane Domains (Lipid Rafts)

Donati

Rasenick

2005

Neuropsychopharmacol

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Previous studies demonstrated that Gsa migrates from a Triton X-100 (TTX-100) insoluble membrane domain to a TTX-100 soluble membrane domain in response to chronic treatment with the antidepressants desipramine and fluoxetine. Antidepressant treatment also causes a Gsa redistribution in cells as seen by confocal microscopy. The current studies have focused on examining the possibility that the association between Gsa and the plasma membrane and/or cytoskeleton is altered in response to antidepressant treatment, and that this is relevant to both Gsa redistribution and the increased coupling between Gsa and adenylyl cyclase seen after chronic antidepressant treatment. Chronic treatment of C6 cells with two fuctionally and structurally distinct antidepressants, desipramine and fluoxetine, decreased the Gsa content of TTX-100 insoluble membrane domains by as much as 60%, while the inactive fluoxetine analog LY368514 had no effect. Disruption of these membrane domains with the cholesterol chelator methyl-b-cyclodextrin altered the localization of many proteins involved in the cAMP signaling cascade, but only Gsa localization was altered by antidepressant treatment. In addition, microtubule disruption with colchicine elicited the movement of Gsa out of detergent-resistant membrane domains in a manner identical to that seen with antidepressant treatment. The data presented here further substantiate the role of Gsa as a major player in antidepressant-induced modification of neuronal signaling and also raise the possibility that an interaction between Gsa and the cytoskeleton is involved in this process.

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Glycolipid‐Enriched Caveolae and Caveolae‐Like Domains in the Nervous System

Cited by 104 publications

References 120 publications

Caveolin proteins and estrogen signaling in the brain

Caveolin proteins and estrogen signaling in the brain

Lipid Raft Disruption Triggers Protein Kinase C and Src-dependent Protein Kinase D Activation and Kidins220 Phosphorylation in Neuronal Cells

Chronic Antidepressant Treatment Prevents Accumulation of Gsα in Cholesterol-Rich, Cytoskeletal-Associated, Plasma Membrane Domains (Lipid Rafts)

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