Role of Lipid Microdomains in P/Q-type Calcium Channel (Cav2.1) Clustering and Function in Presynaptic Membranes

Taverna, Elena; Saba, Elena; Rowe, Joanna; Francolini, Maura; Clementi, Francesco; Rosa, Patrizia

doi:10.1074/jbc.m308798200

Cited by 126 publications

(116 citation statements)

References 44 publications

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“…However, we found no major synaptic deficits in both null-mutants. This is quite surprising, in view of studies suggesting a synaptic role for gangliosides on the basis of exogenous ganglioside application (Tanaka et al, 1997;Ando et al, 1998), as well as the reported co-localization in lipid rafts of gangliosides and proteins important for neuroexocytosis (Chamberlain et al, 2001;Lang et al, 2001;Taverna et al, 2004;Salaun et al, 2004). The only changes we observed were some extra degree of rundown of transmitter release at high intensity use at the dKO NMJ and a temperature-specific increase in quantal content at 35 C in GD3s-KO NMJs, compared to WT.…”

Section: Discussioncontrasting

confidence: 45%

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Neuromuscular synaptic function in mice lacking major subsets of gangliosides

et al. 2008

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Section: Discussioncontrasting

confidence: 45%

“…Several important proteins of the release machinery co-localize with gangliosides within lipid rafts (Chamberlain et al, 2001;Lang et al, 2001;Taverna et al, 2004;Salaun et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

et al. 2008

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“…Gangliosides may be particularly important in synaptic function because they 1) show high expression at synapses (Ando et al, 2004;Waki et al, 1994); 2) co-localize with neuroexocytotic proteins (Chamberlain et al, 2001;Lang et al, 2001;Salaun et al, 2004;Taverna et al, 2004) and 3) influence neurotransmitter release and synaptic plasticity when applied exogenously Egorushkina et al, 1993;Furuse et al, 1998;Ramirez et al, 1990;Tanaka et al, 1997;Wieraszko and Seifert, 1985). In spite of this, we recently showed near-normal synapse function at neuromuscular junctions (NMJs) of mice lacking either complex gangliosides, b/c-series gangliosides or all gangliosides except GM3 ( Fig.1) (Bullens et al, 2002;Zitman et al, 2008), suggesting neurotransmission was supported by GM3 alone or, alternatively, is ganglioside-independent.…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

Zitman

Todorov

Verschuuren

et al. 2011

Neurobiology of Aging

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Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 months-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O-and aseries gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice. AbbreviationsACh, acetylcholine; AChR, acetylcholine receptor; EPP, endplate potential; GD3s-KO, α2,8-sialyltransferase knockout; GM2s-KO, β1,4-GalNAc-transferase knockout; MEPP, miniature endplate potential; NMJ, neuromuscular junction; WT, wild-type.Zitman et al., Synaptic function in aged ganglioside-deficient mice 3

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“…The localization of the calcium/calmodulin-dependent protein Takemoto-Kimura et al 2007). Furthermore, calcium channel localization within lipid rafts in neurons from the cerebellum regulates channel conductance (Taverna et al 2004;Davies et al 2006). Recently, the NMDA receptor was found increasingly associated with lipid rafts in the rat brain during development (Besshoh et al 2007).…”

Section: Function Of Lipid Rafts In Neural Cellsmentioning

confidence: 99%

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Romanelli

Wood²

2008

Journal of Neurochemistry

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The trafficking of receptor tyrosine kinases (RTKs) to distinct subcellular locations is essential for the specificity and fidelity of signal transduction and biological responses. This is particularly important in the PNS and CNS in which RTKs mediate key events in the development and maintenance of neurons and glia through a wide range of neural processes, including survival, proliferation, differentiation, neurite outgrowth, and synaptogenesis. The mechanisms that regulate the targeting of RTKs to their subcellular destinations for appropriate signal transduction, however, are still elusive. In this review, we discuss evidence for the spatial organization of signaling machinery into distinct subcellular compartments, as well as the role for ligand specificity, receptor sorting signals, and lipid raft microdomains in RTK targeting and the resultant cellular responses in neural cells.

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Role of Lipid Microdomains in P/Q-type Calcium Channel (Cav2.1) Clustering and Function in Presynaptic Membranes

Cited by 126 publications

References 44 publications

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

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