Calcineurin inhibition of dynamin I GTPase activity coupled to nerve terminal depolarization

Science ◽  
1994 ◽  
Vol 265 (5174) ◽  
pp. 970-973 ◽  
Author(s):  
J. Liu ◽  
A. Sim ◽  
P. Robinson
Keyword(s):  
Nerve Terminal ◽  
Gtpase Activity ◽  
Dynamin I ◽  
Calcineurin Inhibition

scholarly journals Ubiquitously Expressed Dynamin-II Has a Higher Intrinsic GTPase Activity and a Greater Propensity for Self-assembly Than Neuronal Dynamin-I

1997 ◽  
Vol 8 (12) ◽  
pp. 2553-2562 ◽  
Author(s):  
Dale E. Warnock ◽  
Takeshi Baba ◽  
Sandra L. Schmid
Keyword(s):  
Self Assembly ◽  
Intrinsic Rate ◽  
Biochemical Properties ◽  
Gtpase Activity ◽  
Coated Pits ◽  
Gtp Hydrolysis ◽  
Rich Domain ◽  
Dynamin I ◽  
Intrinsic Gtpase Activity

To begin to understand mechanistic differences in endocytosis in neurons and nonneuronal cells, we have compared the biochemical properties of the ubiquitously expressed dynamin-II isoform with those of neuron-specific dynamin-I. Like dynamin-I, dynamin-II is specifically localized to and highly concentrated in coated pits on the plasma membrane and can assemble in vitro into rings and helical arrays. As expected, the two closely related isoforms share a similar mechanism for GTP hydrolysis: both are stimulated in vitro by self-assembly and by interaction with microtubules or the SH3 domain-containing protein, grb2. Deletion of the C-terminal proline/arginine-rich domain from either isoform abrogates self-assembly and assembly-dependent increases in GTP hydrolysis. However, dynamin-II exhibits a ∼threefold higher rate of intrinsic GTP hydrolysis and higher affinity for GTP than dynamin-I. Strikingly, the stimulated GTPase activity of dynamin-II can be >40-fold higher than dynamin-I, due principally to its greater propensity for self-assembly and the increased resistance of assembled dynamin-II to GTP-triggered disassembly. These results are consistent with the hypothesis that self-assembly is a major regulator of dynamin GTPase activity and that the intrinsic rate of GTP hydrolysis reflects a dynamic, GTP-dependent equilibrium of assembly and disassembly.

Calcium Binds Dynamin I and Inhibits Its GTPase Activity

2002 ◽  
Vol 66 (5) ◽  
pp. 2074-2081 ◽  
Author(s):  
Jun-Ping Liu ◽  
Qun-Xing Zhang ◽  
Graham Baldwin ◽  
Phillip J. Robinson
Keyword(s):  
Gtpase Activity ◽  
Dynamin I

Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity: Competitive Inhibition at the Pleckstrin Homology Domain

2016 ◽  
Vol 60 (1) ◽  
pp. 349-361 ◽  
Author(s):  
Luke R. Odell ◽  
Mohammed K. Abdel-Hamid ◽  
Timothy A. Hill ◽  
Ngoc Chau ◽  
Kelly A. Young ◽  
...  
Keyword(s):  
Competitive Inhibition ◽  
Pleckstrin Homology Domain ◽  
Gtpase Activity ◽  
Pleckstrin Homology ◽  
Dynamin I

1,8-Naphthalimide derivatives: new leads against dynamin I GTPase activity

2015 ◽  
Vol 13 (29) ◽  
pp. 8016-8028 ◽  
Author(s):  
Mohammed K. Abdel-Hamid ◽  
Kylie A. Macgregor ◽  
Luke R. Odell ◽  
Ngoc Chau ◽  
Anna Mariana ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Pocket ◽  
Gtpase Activity ◽  
Gtp Binding ◽  
Dynamin I

Fragment-basedin silicoscreening against dynamin I (dynI) GTPase activity identified the 1,8-naphthalimide framework as a potential scaffold for the design of new inhibitors targeting the GTP binding pocket of dynI.

scholarly journals Syndapin I, a Synaptic Dynamin-binding Protein that Associates with the Neural Wiskott-Aldrich Syndrome Protein

1999 ◽  
Vol 10 (2) ◽  
pp. 501-513 ◽  
Author(s):  
Britta Qualmann ◽  
Jack Roos ◽  
Paul J. DiGregorio ◽  
Regis B. Kelly
Keyword(s):  
Synaptic Vesicle ◽  
Nerve Terminal ◽  
Specific Interaction ◽  
Sh3 Domain ◽  
High Molecular Weight Complex ◽  
Wiskott Aldrich Syndrome ◽  
C Terminus ◽  
Dynamin I ◽  
Syndrome Protein

The GTPase dynamin has been clearly implicated in clathrin-mediated endocytosis of synaptic vesicle membranes at the presynaptic nerve terminal. Here we describe a novel 52-kDa protein in rat brain that binds the proline-rich C terminus of dynamin. Syndapin I (synaptic, dynamin-associated protein I) is highly enriched in brain where it exists in a high molecular weight complex. Syndapin I can be involved in multiple protein–protein interactions via a src homology 3 (SH3) domain at the C terminus and two predicted coiled-coil stretches. Coprecipitation studies and blot overlay analyses revealed that syndapin I binds the brain-specific proteins dynamin I, synaptojanin, and synapsin I via an SH3 domain-specific interaction. Coimmunoprecipitation of dynamin I with antibodies recognizing syndapin I and colocalization of syndapin I with dynamin I at vesicular structures in primary neurons indicate that syndapin I associates with dynamin I in vivo and may play a role in synaptic vesicle endocytosis. Furthermore, syndapin I associates with the neural Wiskott-Aldrich syndrome protein, an actin-depolymerizing protein that regulates cytoskeletal rearrangement. These characteristics of syndapin I suggest a molecular link between cytoskeletal dynamics and synaptic vesicle recycling in the nerve terminal.

scholarly journals Dynamin I phosphorylation and the control of synaptic vesicle endocytosis.

2005 ◽  
Vol 72 ◽  
pp. 87-97 ◽  
Author(s):  
Karen J. Smillie ◽  
Michael A. Cousin
Keyword(s):  
Synaptic Vesicle ◽  
Nerve Terminal ◽  
Current Knowledge ◽  
Direct Proof ◽  
Nerve Terminals ◽  
Cyclin Dependent Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Dynamin I ◽  
Cyclin Dependent Kinase 5

The GTPase dynamin I is essential for synaptic vesicle endocytosis in nerve terminals. It is a nerve terminal phosphoprotein that is dephosphorylated on nerve terminal stimulation by the calcium-dependent protein phosphatase calcineurin and then rephosphorylated by cyclin-dependent kinase 5 on termination of the stimulus. Because of its unusual phosphorylation profile, the phosphorylation status of dynamin I was assumed to be inexorably linked to synaptic vesicle endocytosis; however, direct proof of this link has been elusive until very recently. This review will describe current knowledge regarding dynamin I phosphorylation in nerve terminals and how this regulates its biological function with respect to synaptic vesicle endocytosis.

Small Molecule Inhibitors of Dynamin I GTPase Activity:  Development of Dimeric Tyrphostins

2005 ◽  
Vol 48 (24) ◽  
pp. 7781-7788 ◽  
Author(s):  
Timothy Hill ◽  
Luke R. Odell ◽  
Jennifer K. Edwards ◽  
Mark E. Graham ◽  
Andrew B. McGeachie ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Gtpase Activity ◽  
Dynamin I
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