References of "The Journal of cell biology"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailLiprin-alpha2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission.
Spangler, Samantha A.; Schmitz, Sabine UL; Kevenaar, Josta T. et al

in The Journal of cell biology (2013), 201(6), 915-28

The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold ... [more ▼]

The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-alpha2 as a key organizer in this process. We show that liprin-alpha2 levels were regulated by synaptic activity and the ubiquitin-proteasome system. Furthermore, liprin-alpha2 organized presynaptic ultrastructure and controlled synaptic output by regulating synaptic vesicle pool size. The presence of liprin-alpha2 at presynaptic sites did not depend on other active zone scaffolding proteins but was critical for recruitment of several components of the release machinery, including RIM1 and CASK. Fluorescence recovery after photobleaching showed that depletion of liprin-alpha2 resulted in reduced turnover of RIM1 and CASK at presynaptic terminals, suggesting that liprin-alpha2 promotes dynamic scaffolding for molecular complexes that facilitate synaptic vesicle release. Therefore, liprin-alpha2 plays an important role in maintaining active zone dynamics to modulate synaptic efficacy in response to changes in network activity. [less ▲]

Detailed reference viewed: 45 (6 UL)
Full Text
Peer Reviewed
See detailMunc13 controls the location and efficiency of dense-core vesicle release in neurons.
van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine UL et al

in The Journal of cell biology (2012), 199(6), 883-91

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent ... [more ▼]

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically. [less ▲]

Detailed reference viewed: 55 (2 UL)
Full Text
Peer Reviewed
See detailDendritic position is a major determinant of presynaptic strength.
de Jong, Arthur P. H.; Schmitz, Sabine UL; Toonen, Ruud F. G. et al

in The Journal of cell biology (2012), 197(2), 327-37

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with ... [more ▼]

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent. [less ▲]

Detailed reference viewed: 55 (2 UL)
Full Text
Peer Reviewed
See detailThe plasmamembrane calmodulin-dependent calcium pump: a major regulator of nitric oxide synthase I.
Schuh, K.; Uldrijan, S.; Telkamp, M. et al

in The Journal of cell biology (2001), 155(2), 201-5

The plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA) (Shull, G.E., and J. Greeb. 1988. J. Biol. Chem. 263:8646-8657; Verma, A.K., A.G. Filoteo, D.R. Stanford, E.D. Wieben, J.T. Penniston ... [more ▼]

The plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA) (Shull, G.E., and J. Greeb. 1988. J. Biol. Chem. 263:8646-8657; Verma, A.K., A.G. Filoteo, D.R. Stanford, E.D. Wieben, J.T. Penniston, E.E. Strehler, R. Fischer, R. Heim, G. Vogel, S. Mathews, et al. 1988. J. Biol. Chem. 263:14152-14159; Carafoli, E. 1997. Basic Res. Cardiol. 92:59-61) has been proposed to be a regulator of calcium homeostasis and signal transduction networks of the cell. However, little is known about its precise mechanisms of action. Knock-out of (mainly neuronal) isoform 2 of the enzyme resulted in hearing loss and balance deficits due to severe inner ear defects, affecting formation and maintenance of otoconia (Kozel, P.J., R.A. Friedman, L.C. Erway, E.N. Yamoah, L.H. Liu, T. Riddle, J.J. Duffy, T. Doetschman, M.L. Miller, E.L. Cardell, and G.E. Shull. 1998. J. Biol. Chem. 273:18693-18696). Here we demonstrate that PMCA 4b is a negative regulator of nitric oxide synthase I (NOS-I, nNOS) in HEK293 embryonic kidney and neuro-2a neuroblastoma cell models. Binding of PMCA 4b to NOS-I was mediated by interaction of the COOH-terminal amino acids of PMCA 4b and the PDZ domain of NOS-I (PDZ: PSD 95/Dlg/ZO-1 protein domain). Increasing expression of wild-type PMCA 4b (but not PMCA mutants unable to bind PDZ domains or devoid of Ca2+-transporting activity) dramatically downregulated NO synthesis from wild-type NOS-I. A NOS-I mutant lacking the PDZ domain was not regulated by PMCA, demonstrating the specific nature of the PMCA-NOS-I interaction. Elucidation of PMCA as an interaction partner and major regulator of NOS-I provides evidence for a new dimension of integration between calcium and NO signaling pathways. [less ▲]

Detailed reference viewed: 58 (1 UL)
Peer Reviewed
See detailFunctional differences between L- and T-plastin isoforms.
Arpin, M.; Friederich, Evelyne UL; Algrain, M. et al

in The Journal of cell biology (1994), 127(6 Pt 2), 1995-2008

Fimbrins/plastins are a family of highly conserved actin-bundling proteins. They are present in all eukaryotic cells including yeast, but each isoform displays a remarkable tissue specificity. T-plastin ... [more ▼]

Fimbrins/plastins are a family of highly conserved actin-bundling proteins. They are present in all eukaryotic cells including yeast, but each isoform displays a remarkable tissue specificity. T-plastin is normally found in epithelial and mesenchymal cells while L-plastin is present in hematopoietic cells. However, L-plastin has been also found in tumor cells of non-hematopoietic origin (Lin, C.-S., R. H. Aebersold, S. B. Kent, M. Varma, and J. Leavitt. 1988. Mol. Cell. Biol. 8:4659-4668; Lin, C.-S., R. H. Aebersold, and J. Leavitt. 1990. Mol. Cell. Biol. 10: 1818-1821). To learn more about the biological significance of their tissue specificity, we have overproduced the T- and L-plastin isoforms in a fibroblast-like cell line, CV-1, and in a polarized epithelial cell line, LLC-PK1. In CV-1 cells, overproduction of T- and L-plastins induces cell rounding and a concomitant reorganization of actin stress fibers into geodesic structures. L-plastin remains associated with microfilaments while T-plastin is almost completely extracted after treatment of the cells with non-ionic detergent. In LLC-PK1 cells, T-plastin induces shape changes in microvilli and remains associated with microvillar actin filaments after detergent extraction while L-plastin has no effect on these structures and is completely extracted. The effect of T-plastin on the organization of microvilli differs from that of villin, another actin-bundling protein. Our experiments indicate that these two isoforms play differing roles in actin filament organization, and do so in a cell type-specific fashion. Thus it is likely that these plastin isoforms play fundamentally different roles in cell function. [less ▲]

Detailed reference viewed: 54 (0 UL)
Peer Reviewed
See detailIn vivo analysis of functional domains from villin and gelsolin.
Finidori, J.; Friederich, Evelyne UL; Kwiatkowski, D. J. et al

in The Journal of cell biology (1992), 116(5), 1145-55

Transfected CV1 cells were used to compare the in vivo effects of various domains of villin and gelsolin. These two homologous actin modulating proteins both contain a duplicated severin-like sequence ... [more ▼]

Transfected CV1 cells were used to compare the in vivo effects of various domains of villin and gelsolin. These two homologous actin modulating proteins both contain a duplicated severin-like sequence. Villin has in addition a carboxy-terminal domain, the headpiece, which accounts for its bundling activity. The effects of the villin-deleted mutants were compared with those of native villin. Our results show that essential domains of villin required to induce the growth of microvilli and F-actin redistribution are present in the first half of the core and in the headpiece. We also show that the second half of the villin core cannot be exchanged by its homolog in gelsolin. When expressed at high levels of CV1 cells, full length gelsolin completely disrupted stress fibers without change of the cell shape. Addition of the villin headpiece to gelsolin had no effect on the phenotype induced by gelsolin alone. Expression of the first half of gelsolin induced similar modifications as capping proteins and rapid cell mortality; this deleterious effect on the cell structure was also observed when the headpiece was linked to the first half of gelsolin. In cells expressing the second half of gelsolin, a dotted F-actin staining was often seen. Moreover elongated dorsal F-actin structures were observed when the headpiece was linked to the second gelsolin domain. These studies illustrate the patent in vivo severing activity of gelsolin as well as the distinct functional properties of villin core in contrast to gelsolin. [less ▲]

Detailed reference viewed: 50 (0 UL)