• Because of its potential importance in acinar cell digestive enzyme secretion Rab3 is an important subject for review. (pancreapedia.org)
  • These findings show that EPI64B plays a role in regulating secretion in pancreatic acinar cells and that Rab27B turnover takes on an important part in acinar cell secretion. (research-in-field.com)
  • These include four regions participating in guanine nucleotide binding, and effector region corresponding to the effector region in Ras, and a CXC prenylation motif at the C-terminal (45). (pancreapedia.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)
  • 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)
  • Presynaptic active zone proteins have a crucial role in regulating vesicle exocytosis, which is essential for synaptic plasticity. (jneurosci.org)
  • Here, after research involving Sprague Dawley rats, we reported that spinal nerve ligation (SNL), in addition to causing allodynia, enhances the Rab3-interactive molecule-1α (RIM1α), a major active zone protein presumed to regulate neural plasticity, specifically in the synaptic plasma membranes (SPMs) of the ipsilateral dorsal horn. (jneurosci.org)
  • Studies investigating pain pathology have demonstrated that ubiquitination contributes to chronic pain by regulating the turnover of synaptic proteins. (jneurosci.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)
  • There are no known GEFs specific for individual Rab3 isoforms such as Rab3D. (pancreapedia.org)
  • There is one known Rab3 GAP which acts on all four Rab3 isoforms and is broadly distributed in different tissues (26). (pancreapedia.org)
  • 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)
  • 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)
  • Rab3GEP/MADD was shown to be a nonredundant GEF for Rab27A activation in melanocytes (25) as well as a GEF for all four Rab3 isoforms (26). (research-in-field.com)
  • 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)
  • We propose that PIP2, through the control of Crag's subcellular localization, restricts the secretion of BM proteins to the basal side. (princeton.edu)
  • 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)
  • 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)
  • Knowledge about protein localization in Golgi compartments is largely based on work in cell lines. (bvsalud.org)
  • The tiny GTPase Rab27B localizes to the zymogen granule membranes and plays an important role in regulating protein secretion by pancreatic acinar cells as does Rab3D. (research-in-field.com)
  • As a secretory small GTPase, Rab3D is a vital regulator for protein secretion. (oncotarget.com)
  • The GTPase Rab11 regulates endosomal protein trafficking and previous work has shown that loss of Rab11 caused intestinal inflammation and hyperplasia in mice and flies. (sdbonline.org)
  • In the tumor microenvironment, cell migration and invasion are regulated by many factors such as intracellular signaling pathways, growth factors or onco-proteins [ 2 ]. (oncotarget.com)
  • Rab GTPases, as intracellular transport proteins, are master regulators of exocytic and endocytic membrane trafficking [ 10 ]. (oncotarget.com)
  • Here, we identify phosphatidylino-sitol 4,5-bisphosphate (PIP2) as a critical regulator of the polarized secretion of BM proteins. (princeton.edu)
  • The crystal structure of Rab3A in the active configuration or bound to Rabphillin has been determined (19, 50) and Rab3D has been fit to the same model with 6 β-strands and 5 α-helices (45). (pancreapedia.org)
  • EPI64B almost completely abolished the GTP-bound form of Rab27B without influencing GTP-Rab3D. (research-in-field.com)
  • Overexpression of EPI64B in isolated mouse acini specifically inhibited the activation of exogenous and endogenous Rab27B but not Rab3D or additional closely related small G proteins involved in secretion. (research-in-field.com)
  • We detected protein levels of Rab3D in nine cancer cell lines and twelve types of clinical cancer specimens. (oncotarget.com)
  • A decrease of PIP2 levels, in particular through mutations in Phosphatidylinositol synthase (Pis) and other members of the phosphoinositide pathway, leads to the aberrant accumulation of BM components at the apical side of the cell without primarily affecting the distribution of apical and basolateral polarity proteins. (princeton.edu)
  • Rab proteins constitute the largest family of Ras-related small G proteins and play a role in regulating the specificity of membrane trafficking (63, 78). (pancreapedia.org)
  • Abundant proteins, including membrane trafficking molecules, cytoskeleton molecules, chaperones, signal transduction proteins and cytoplasmic enzymes have been included in secreted exosomes [ 9 ]. (oncotarget.com)
  • These data highlight the importance of membrane protein recycling during development. (sdbonline.org)
  • As a result we hypothesized that EPI64 subfamily proteins(s) would have potential Rab27B-Difference activity in pancreatic acinar cells. (research-in-field.com)
  • Isolation Viral Illness of Pancreatic Acini and Analysis of Amylase Secretion Pancreatic acini were isolated from 5-7-week-old male ICR mice by collagenase digestion as explained previously (33 34 Isolated acini were resuspended in Dulbecco's revised Eagle's medium (DMEM) comprising 0.1% BSA 0.02% soybean trypsin inhibitor and antibiotics and incubated at 37 °C inside a tissue tradition incubator with 5% CO2 for 16 h. (research-in-field.com)
  • 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)
  • Tomosyn is a large, non-canonical SNARE protein proposed to act as an inhibitor of SNARE complex formation in the exocytosis of secretory vesicles. (bvsalud.org)
  • 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)
  • The different secretory processes are controlled by corresponding Rab proteins including Rab3A/B/C/D, Rab26, Rab27A/B and Rab37. (oncotarget.com)
  • Structurally, Rab3 species contain conserved functional domains similar to other Rabs. (pancreapedia.org)
  • First is the disruption of enterocyte polarity based on staining of the FERM domain protein Coracle . (sdbonline.org)
  • Spinal plasticity, a key process mediating neuropathic pain development, requires ubiquitination-dependent protein turnover. (jneurosci.org)
  • Nevertheless, the mechanism for ubiquitination-regulated turnover of presynaptic active zone proteins in the progression of spinal plasticity-associated neuropathic pain remains unclear. (jneurosci.org)
  • SIGNIFICANCE STATEMENT Ubiquitination is a well known process required for protein degradation. (jneurosci.org)
  • In addition, Fbxo3 modifies this pathway by inhibiting Fbxl2-mediated RIM1α ubiquitination, suggesting that presynaptic protein ubiquitination makes a crucial contribution to the development of neuropathic pain. (jneurosci.org)
  • To test the idea that loss of Rab11 may promote cancer progression, archival human patient tissues were analyzed and 51 out of 70 colon cancer tissues had lower Rab11 protein staining. (sdbonline.org)
  • In contrast, loss of the specific subunits of TRAPPII, another known Rab11-GEF, does not cause any defects on the eye development nor the transport of rhabdomere proteins, however, simultaneous loss of TRAPPII and Pcs shows severe defects on eye development. (sdbonline.org)
  • Subsequent molecular cloning revealed four members of the Rab3 family termed 3A (the form originally found in brain), 3B, 3C, and 3D. (pancreapedia.org)
  • The present study unravels a new molecular system for vesicle-based axonal transport of proteins in male and female flies (Drosophila melanogaster). (sdbonline.org)
  • Subsequently, following deubiquitination, enhanced RIM1α directly binds to CaV2.2, resulting in increased CaV2.2 expression in the SPMs of the dorsal horn. (jneurosci.org)
  • Here, we found that the spinal presynaptic active zone protein Rab3-interactive molecule-1α (RIM1α) participates in neuropathic pain development by binding to and upregulating the expression of Ca V 2.2. (jneurosci.org)
  • In addition together with Rab27A Rab27B was shown to control different methods of the exosome secretion pathway (24). (research-in-field.com)
  • Two TBC proteins EPI64/TBC1D10A and EPI64B/TBC1D10B/FLJ13130 have already been identified as Spaces for Rab27A in melanocytes (28). (research-in-field.com)
  • Likewise, Rab Escort Protein plays a role in the recycling of many or all Rab proteins (2). (pancreapedia.org)
  • Our findings identify a role of the presynaptic active zone protein in pain-associated plasticity. (jneurosci.org)
  • Violin plots show distribution of expression levels for Ras-related protein Rab-27A (SMED30022570) in cells (dots) of each of the 12 neoblast clusters. (stowers.org)
  • Expression of Ras-related protein Rab-27A (SMED30022570) in the t-SNE clustered sub-lethally irradiated X1 and X2 cells. (stowers.org)
  • Mutations that block the Space activity decreased the inhibitory effect of EPI64B within the GTP-bound state of Rab27B and abolished the enhancing effect of EPI64B within the amylase launch. (research-in-field.com)
  • Ras-related protein Rab-3B is a protein that in humans is encoded by the RAB3B gene. (wikipedia.org)
  • A number of studies have shown that Rab27B plays a critical part in the secretion in melanocytes (13 14 platelets (15) urothelial umbrella cells (16) mast cells (17) pituitary endocrine cells (18) parietal cells (19) neutrophils (20) BTZ043 parotid (21 22 and lacrimal (23) acinar cells. (research-in-field.com)
  • Rab3 GEP is identical to the human DENN/MADD protein and contains a death domain which can bind the TNFR1 (15). (pancreapedia.org)
  • The latter is used for the addition of two geranylgeranyl groups to the cysteine residues which attach the Rab3 to membranes (35). (pancreapedia.org)
  • In addition, it also regulated the extracellular secretion of Hsp90α to promote tumor cell migration and invasion. (oncotarget.com)
  • The Rab27B-Space activity and secretion-enhancing effect of EPI64 were dependent on the TBC website. (research-in-field.com)
  • 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)