Hence, RIM plays an evolutionarily conserved role in regulating synaptic calcium channel localization and readily releasable pool size. (jneurosci.org)
These effects are accompanied by imbalances in the activity of specific prenylated proteins, Rab3 and RhoA, involved in neurotransmitter release, and synaptic plasticity, respectively. (nature.com)
However, the synaptic phenotype in the rab3-GEF mutant cannot be fully explained by defective transport and loss of GEF activity. (eneuro.org)
Rab3 was originally identified in brain and shown to be localized to synaptic vesicles (24). (pancreapedia.org)
Rab3 GEP knockout mice die at birth and embryonic synaptic transmitter release is impaired (64). (pancreapedia.org)
Prenylation, the covalent binding of farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) moieties to proteins, is a crucial post-translational modification for the regulation of protein localization on cell membranes and, in turn, for key cellular processes. (nature.com)
At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. (eneuro.org)
Similar to other small G proteins, the guanine binding state of Rab3 proteins is regulated by guanine nucleotide exchange proteins or factors (GEPs or GEFs) and GTPase activating proteins (GAPs). (pancreapedia.org)
We propose that PIP2, through the control of Crag's subcellular localization, restricts the secretion of BM proteins to the basal side. (princeton.edu)
Loss of Pcs impairs Rab11 localization on the trans-side of Golgi units and induces the cytoplasmic accumulation of post-Golgi vesicles bearing rhabdomere proteins, as observed in Rab11-deficiency. (sdbonline.org)
Effector5
Because RIM has traditionally been studied as an effector of Rab3 function, we investigate whether RIM is involved in the newly identified function of Rab3 in the distribution of presynaptic release machinery components across release sites. (jneurosci.org)
In addition, larvae containing mutations in both RIM and rab3 have reduced Ca 2+ channel levels and a Brp distribution that is very similar to that of the rab3 single mutant, indicating that RIM functions to regulate Ca 2+ channel accumulation but is not a Rab3 effector for release machinery distribution across release sites. (jneurosci.org)
In rodents and C. elegans , RIM binds to and is an effector of the small GTPase Rab3. (jneurosci.org)
Our results suggest that although Rab3-GEF acts upstream of Rab3 to control Rab3 localization and likely GTP-binding, it also acts downstream to regulate CAZ development, potentially as a Rab3 effector at the synapse. (eneuro.org)
Our studies reveal that Rab3 and Rab3-GEF act within the same molecular mechanism and support a model wherein Rab3-GEF serves as a Rab3 effector to control active zone protein composition. (eneuro.org)
Secretion5
Because of its potential importance in acinar cell digestive enzyme secretion Rab3 is an important subject for review. (pancreapedia.org)
Because of its localization and homology to the yeast protein Sec4, it was believed to play a role in the terminal steps of secretion. (pancreapedia.org)
Rab3 isoforms have been identified in different tissues and cell types where it has been suggested to play a role in secretion (Table 1). (pancreapedia.org)
Note that in some cases Rab3 inhibits and in others it stimulates secretion. (pancreapedia.org)
In addition, PIP2 controls the apical and lateral localization of Crag (Calmodulin-binding protein related to a Rab3 GDP/GTP exchange protein), a factor specifically required to prevent aberrant apical secretion of BM. (princeton.edu)
Neurotransmitter release1
A single form of Rab3 exists in C. elegans and is believed to play a role in neurotransmitter release (47), while in sea urchin eggs a Rab3 is believed to play a role in cortical granule exocytosis (13). (pancreapedia.org)
Stimulates1
As the Drosophila homologue of mammalian DENN/MADD and Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor (GEF) for Rab3 that stimulates GDP to GTP exchange. (eneuro.org)
Drosophila2
Here we identify Drosophila RIM (Rab3 interacting molecule) and demonstrate that it localizes to active zones at the larval neuromuscular junction. (jneurosci.org)
We show here that Rab3-GEF is required for controlling the protein composition of release sites in the Drosophila neuromuscular junction (NMJ). (eneuro.org)
Mutant3
At rab3-GEF mutant NMJs, Bruchpilot (Brp) and Ca 2+ channels are enriched at a subset of AZs, leaving the remaining sites devoid of key CAZ components in a manner that is indistinguishable from rab3 mutant NMJs. (eneuro.org)
A transgenically expressed GTP-locked variant of Rab3 accumulates at the NMJ at wild-type levels and fully rescues the rab3 mutant but is unable to rescue the rab3-GEF mutant. (eneuro.org)
The structure of the Rabs changes upon binding GTP and mutant Rab3 species have been described similar to Ras that are locked into active and inactive configurations (6). (pancreapedia.org)
Rab3A2
Rab3 GEP was purified from brain and acted on Rab3A, 3C and 3D (72). (pancreapedia.org)
The second Rab3 GEF, known as GRAB, interacts with inositol hexakisphosphate kinase and Rab3A and its protein expression is primarily in brain (41). (pancreapedia.org)
MADD1
Rab3 GEP is identical to the human DENN/MADD protein and contains a death domain which can bind the TNFR1 (15). (pancreapedia.org)
Regulation1
RAB3GAP, which is involved in regulation of RAB3 activity, is a heterodimeric complex consisting a 130-kD catalytic subunit and a 150-kD noncatalytic subunit (MIM 609275). (novusbio.com)
Protein composition1
Here we identify Rab3-GEF as a second protein that acts in conjunction with Rab3 to control AZ protein composition. (eneuro.org)
Molecular1
Subsequent molecular cloning revealed four members of the Rab3 family termed 3A (the form originally found in brain), 3B, 3C, and 3D. (pancreapedia.org)
Form1
RAB3GAP specifically converts active RAB3-GTP to the inactive form RAB3-GDP (Aligianis et al. (novusbio.com)
Active1
Bruchpilot (Brp), an essential component of the active zone cytomatrix T bar, is unaffected by RIM disruption, indicating that Brp localization and distribution across active zones does not require wild-type RIM. (jneurosci.org)
Individual1
There are no known GEFs specific for individual Rab3 isoforms such as Rab3D. (pancreapedia.org)
Specific1
There is no known specific Rab3 GDI, but rather a common family of Rab GDI isoforms which bind prenylated Rabs in the cytoplasm and participates in insertion and removal from membranes (75). (pancreapedia.org)
Multiple1
Because of the presence of multiple forms of Rab3 in neuronal cells, the group of T. Sudhof prepared a mouse model in which all four isoforms of Rab3 were deleted. (pancreapedia.org)
Loss2
Our results indicate that loss of Rab3-GEF results in the development of NMJs that are structurally and functionally indistinguishable from NMJs that lack the protein Rab3. (eneuro.org)
Loss of Rab11 also leads to defects in larval dendrite elaboration, and Neuroglian and Ppk26 localization is already altered at this stage. (sdbonline.org)
Acts1
There is one known Rab3 GAP which acts on all four Rab3 isoforms and is broadly distributed in different tissues (26). (pancreapedia.org)
Similar1
Structurally, Rab3 species contain conserved functional domains similar to other Rabs. (pancreapedia.org)
Addition1
The latter is used for the addition of two geranylgeranyl groups to the cysteine residues which attach the Rab3 to membranes (35). (pancreapedia.org)
Protein localization1
In addition, immunoelectron microscopy has been used to provide further information on protein localization. (medscape.com)
Residues2
The latter is used for the addition of two geranylgeranyl groups to the cysteine residues which attach the Rab3 to membranes (35). (pancreapedia.org)
Experiments with deletion/mutation constructs have revealed the importance of amino-terminal domain (46-290) for memory suppression whereas carboxyl domain (598-854) and the amino-terminal residues (1-45) including the nuclear localization signal (NLS1) are dispensable. (sdbonline.org)
Regulatory1
The regulatory region has the cyclic nucleotide-binding domain (CNB), the Desheveled-Egl-10-Pleckstrin (DEP), which is involved in membrane localization. (pancreapedia.org)
Studies1
In addition, co-localization studies have been performed in granule-containing AR42J cells, an acinar model system. (medscape.com)
Common1
There is no known specific Rab3 GDI, but rather a common family of Rab GDI isoforms which bind prenylated Rabs in the cytoplasm and participates in insertion and removal from membranes (75). (pancreapedia.org)
Important1
Because of its potential importance in acinar cell digestive enzyme secretion Rab3 is an important subject for review. (pancreapedia.org)
Release1
We show here that Rab3-GEF is required for controlling the protein composition of release sites in the Drosophila neuromuscular junction (NMJ). (eneuro.org)
Play2
Because of its localization and homology to the yeast protein Sec4, it was believed to play a role in the terminal steps of secretion. (pancreapedia.org)
Rab3 isoforms have been identified in different tissues and cell types where it has been suggested to play a role in secretion (Table 1). (pancreapedia.org)