Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals

Robinson, Phillip J.; Sontag, Jean‐Marie; Liu, Junping; Fykse, Else Marie; Slaughter, Clive A.; McMahontt, Harvey; Südhof, Thomas C.

doi:10.1038/365163a0

Cited by 268 publications

(237 citation statements)

References 20 publications

Supporting

Mentioning

225

Contrasting

Order By: Relevance

“…4, see also Wang et al, 1988;Robinson, 1992). One protein that shows initial dephosphorylation, p96 or dynamin-I, is implicated in endocytosis rather than exocytosis (see Robinson et al, 1993). The present results support earlier findings suggesting that the intrinsically CaZ+-independent phosphatases 1 and 2A are involved in the Ca2+-dependent dephosphorylation upon stimulation (Sim et al, 1991(Sim et al, , 1993.…”

Section: Which Cellular Actions Of Ba 2+ Are Responsible For Its Stimsupporting

confidence: 89%

“…The relevance of protein phosphorylation for the events prior to transmitter release may be questioned. Several recent reports, using a variety of approaches, indicate that the Ca 2 +-dependent phosphorylation of presynaptic proteins may indeed be of limited importance for initiating transmitter release (see Hens et al, 1993;McMahon and Nicholls, 1993;Rosahl et al, 1993).…”

Section: Is Transmitter Release Indeed Independent Of Calmodulin Actimentioning

confidence: 99%

See 1 more Smart Citation

Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphatases and in exocytosis of all major transmitters

Verhage

Hens

Graan

et al. 1995

European Journal of Pharmacology: Molecular Pharmacology

View full text Add to dashboard Cite

Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractExocytosis from nerve terminals is triggered by depolarization-evoked Ca*+ entry, which also activates calmodulin and stimulates protein phosphorylation. Ba2+ is believed to replace Ca2+ m triggering exocytosis without activation of calmodulin and can therefore be '+ used to unravel aspects of presynaptic function. We have analysed the cellular actions of Ba in relation to its effect on transmitter release from isolated nerve terminals. Barium evoked specific release of amino acid transmitters, catecholamines and neuropeptides (EC,, 0.2-0.5 mM), similar to K'/Ca" -evoked release both in extent and kinetics. Ba2 +-and Ca2+ -evoked release were not additive. In contrast to Ca'+, Ba2+ triggered release which was insensitive to trifluoperizine and hardly stimulated protein phosphorylation. These observations are in accordance with the ability of Ba2+ to replace CaZf m exocytosis without activating calmodulin. Nevertheless, calmodulin appears to be essential for regular (Cazf -triggered) exocytosis, given its sensitivity to trifluoperizine.Both Ba2+-and Ca'+-evoked release were blocked by okadaic acid. Furthermore, anti-calcineurin antibodies decreased Ba'+-evoked release. In conclusion, BaZf replaces Ca'+/calmodulin in the release of the same transmitter pool. Calmodulin-dependent phosphorylation appears not to be essential for transmitter release. Instead, our data implicate both CaZf -dependent and -independent dephosphorylation in the events prior to neurotransmitter exocytosis.Keywords: Exocytosis; Ba*+; Ca'+-dependent release; Calmodulin; Okadaic acid, Phosphatase IntroductionThe regulated exocytosis of neurotransmitters and neuropeptides is triggered by depolarization evoked Ca*+ entry. Although this process is reasonably specific for Ca2+, several divalent cations with similar physico-chemical properties, such as Ba'+, Sr2+ and Pb2+, were found to evoke transmitter release as well (Zengel and Magleby, 1980;Augustine and Eckert, 1984;Heldman et al., 1989;Shao and Suszkiw, 1991;McMahon and Nicholls, 1993;Sihra et al., 1993). Among these, Ba2+ is the best documented and probably the most effective. However, Ba2+ was found to be ineffective in binding and activating the

show abstract

Section: Which Cellular Actions Of Ba 2+ Are Responsible For Its Stimsupporting

confidence: 89%

Section: Is Transmitter Release Indeed Independent Of Calmodulin Actimentioning

confidence: 99%

Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphatases and in exocytosis of all major transmitters

Verhage

Hens

Graan

et al. 1995

European Journal of Pharmacology: Molecular Pharmacology

View full text Add to dashboard Cite

show abstract

“…56 Additionally, DYN-I has also been found to interact with NMDA receptor 1 57 and SNAP-23, 58 closely related to SNAP-25, proteins which have been previously implicated in the pathogenesis of schizophrenia. [59][60][61][62] DYN-I is a GTPase essential for the recovery of synaptic vesicles from the neuronal membrane once the contents have been released 63 and has been hypothesized to have evolved to have a primary role in synaptic vesicle recycling. 64 ), who found that DYN-I and II were increased in the grey matter but decreased in the white matter of schizophrenics in comparison to controls, while a recent proteomics study of the anterior cingulate cortex in schizophrenia also reported an increase in dynamin 1 in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

et al. 2007

View full text Add to dashboard Cite

There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P < 0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.

show abstract

“…These findings provide support to the hypothesis that the long proline-rich COOH-terminal region of dynamin I represents a template for the recruitment of different SH3-containing proteins via highly specific interactions mediated by distinct binding sites. The proline-rich domain of dynamin I undergoes phosphorylation/dephosphorylation (38). It is possible that the phosphorylation of specific amino acid positions may serve to selectively regulate the interactions of dynamin I with one or a subset of SH3 domains.…”

Section: Discussionmentioning

confidence: 99%

The SH3 Domain of Amphiphysin Binds the Proline-rich Domain of Dynamin at a Single Site That Defines a New SH3 Binding Consensus Sequence

Grabs

Slepnev

Songyang

et al. 1997

Journal of Biological Chemistry

250

220

View full text Add to dashboard Cite

Amphiphysin is an SH3 domain-containing neuronal protein that is highly concentrated in nerve terminals where it interacts via its SH3 domain with dynamin I, a GTPase implicated in synaptic vesicle endocytosis. We show here that the SH3 domain of amphiphysin, but not a mutant SH3 domain, bound with high affinity to a single site in the long proline-rich region of human dynamin I, that this site was distinct from the binding sites for other SH3 domains, and that the mutation of two adjacent amino acids in dynamin I was sufficient to abolish binding. The dynamin I sequence critically required for amphiphysin binding (PSRPNR) fits in the novel SH3 binding consensus identified for the SH3 domain of amphiphysin via a combinatorial peptide library approach: PXRPXR(H)R(H). Our data demonstrate that the long proline-rich stretch present in dynamin I contained multiple SH3 domain binding sites that recognize interacting proteins with high specificity.Dynamin I is a neuronal GTPase concentrated in nerve terminals that plays an essential role in synaptic vesicle endocytosis and recycling (for reviews, see Refs. 1 and 2). A temperature-sensitive mutation in the dynamin I gene of Drosophila leads to rapid and massive block of synaptic vesicle endocytosis resulting in a paralytic phenotype (3-5). Ultrastructural studies have shown that dynamin I forms rings at the neck of clathrin-coated pits, and it has been hypothesized that a conformational change of the ring that correlates with GTP hydrolysis represents a key step leading to vesicle fission from the plasmalemma (6, 7). In addition, dynamin I has also been implicated in rapid endocytosis, a form of Ca 2ϩ -triggered endocytosis detectable by capacitance measurement in neuroendocrine cells (8). Dynamin isoforms (dynamin II and dynamin III) are expressed in non-neuronal cells (9 -11) where they are thought to play a general role in clathrin-mediated endocytosis (12, 13).The COOH-terminal region of dynamin I contains a 100-amino acid-long proline-rich domain (14), which undergoes regulation by protein phosphorylation and binds a variety of SH3 domains (13,(15)(16)(17)(18)). An abundant SH3 domain-containing protein, which is a major binding partner for dynamin I in nerve terminals (19), is amphiphysin, the dominant autoantigen in paraneoplastic stiff-man syndrome (20 -22). Amphiphysin is closely colocalized with dynamin I at synapses where, in addition to dynamin I, it binds the presynaptic inositol-5-phosphatase synaptojanin (23). Amphiphysin binds the plasmalemmal clathrin adaptor AP2 via a region distinct from its SH3 domain (19, 24), further supporting an involvement of amphiphysin in endocytosis. In addition, amphiphysin contains regions of similarity to two yeast proteins, Rvs167 and Rvs161 (20,25,26), which genetic studies have shown to be implicated both in endocytosis and in the function of the actin cytoskeleton (26,27).As a premise to further elucidate the functional interconnections between amphiphysin and dynamin I, we investigated regions that are crucial for re...

show abstract

Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals

Cited by 268 publications

References 20 publications

Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphatases and in exocytosis of all major transmitters

Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphatases and in exocytosis of all major transmitters

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

The SH3 Domain of Amphiphysin Binds the Proline-rich Domain of Dynamin at a Single Site That Defines a New SH3 Binding Consensus Sequence

Contact Info

Product

Resources

About