scholarly journals Snapin associates with late endocytic compartments and interacts with late endosomal SNAREs

2009 ◽  
Vol 29 (4) ◽  
pp. 261-269 ◽  
Author(s):  
Li Lu ◽  
Qian Cai ◽  
Jin-Hua Tian ◽  
Zu-Hang Sheng
Keyword(s):  
Membrane Trafficking ◽  
Critical Role ◽  
Degradation Process ◽  
Late Endosome ◽  
Snare Proteins ◽  
Genetic Mouse Model ◽  
Protein Receptor ◽  
Important Regulator ◽  
Endocytic Compartments ◽  
Synaptic Vesicle Fusion

Late endocytic membrane trafficking delivers target materials and newly synthesized hydrolases into lysosomes and is critical for maintaining an efficient degradation process and cellular homoeostasis. Although some features of late endosome–lysosome trafficking have been described, the mechanisms underlying regulation of this event remain to be elucidated. Our previous studies showed that Snapin, as a SNAP25 (25 kDa synaptosome-associated protein)-binding protein, plays a critical role in priming synaptic vesicles for synchronized fusion in neurons. In the present study, we report that Snapin also associates with late endocytic membranous organelles and interacts with the late endosome-targeted SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex. Using a genetic mouse model, we further discovered that Snapin is required to maintain a proper balance of the late endocytic protein LAMP-1 (lysosome-associated membrane protein-1) and late endosomal SNARE proteins syntaxin 8 and Vti1b (vesicle transport through interaction with target SNAREs homologue 1b). Deleting the snapin gene in mice selectively led to the accumulation of these proteins in late endocytic organelles. Thus our present study suggests that Snapin serves as an important regulator of the late endocytic fusion machinery, in addition to its established role in regulating synaptic vesicle fusion.

scholarly journals Regulation of intracellular membrane trafficking and cell dynamics by syntaxin-6

2012 ◽  
Vol 32 (4) ◽  
pp. 383-391 ◽  
Author(s):  
Jae-Joon Jung ◽  
Shivangi M. Inamdar ◽  
Ajit Tiwari ◽  
Amit Choudhury
Keyword(s):  
Membrane Trafficking ◽  
Critical Role ◽  
Cell Types ◽  
Intracellular Membrane ◽  
Cellular Functions ◽  
Cell Dynamics ◽  
Transport Pathways ◽  
Protein Receptor ◽  
Secretory Transport ◽  
Target Membrane

Intracellular membrane trafficking along endocytic and secretory transport pathways plays a critical role in diverse cellular functions including both developmental and pathological processes. Briefly, proteins and lipids destined for transport to distinct locations are collectively assembled into vesicles and delivered to their target site by vesicular fusion. SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins are required for these events, during which v-SNAREs (vesicle SNAREs) interact with t-SNAREs (target SNAREs) to allow transfer of cargo from donor vesicle to target membrane. Recently, the t-SNARE family member, syntaxin-6, has been shown to play an important role in the transport of proteins that are key to diverse cellular dynamic processes. In this paper, we briefly discuss the specific role of SNAREs in various mammalian cell types and comprehensively review the various roles of the Golgi- and endosome-localized t-SNARE, syntaxin-6, in membrane trafficking during physiological as well as pathological conditions.

Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis

2012 ◽  
Vol 92 (4) ◽  
pp. 1915-1964 ◽  
Author(s):  
Haruo Kasai ◽  
Noriko Takahashi ◽  
Hiroshi Tokumaru
Keyword(s):  
Membrane Trafficking ◽  
Synaptic Vesicles ◽  
Cell Types ◽  
Snare Proteins ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Large Dense Core Vesicles ◽  
Sensitive Factor ◽  
The Common ◽  
Kinetics Of

The dynamics of exocytosis are diverse and have been optimized for the functions of synapses and a wide variety of cell types. For example, the kinetics of exocytosis varies by more than five orders of magnitude between ultrafast exocytosis in synaptic vesicles and slow exocytosis in large dense-core vesicles. However, in all cases, exocytosis is mediated by the same fundamental mechanism, i.e., the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is often assumed that vesicles need to be docked at the plasma membrane and SNARE proteins must be preassembled before exocytosis is triggered. However, this model cannot account for the dynamics of exocytosis recently reported in synapses and other cells. For example, vesicles undergo exocytosis without prestimulus docking during tonic exocytosis of synaptic vesicles in the active zone. In addition, epithelial and hematopoietic cells utilize cAMP and kinases to trigger slow exocytosis of nondocked vesicles. In this review, we summarize the manner in which the diversity of exocytosis reflects the initial configurations of SNARE assembly, including trans-SNARE, binary-SNARE, unitary-SNARE, and cis-SNARE configurations. The initial SNARE configurations depend on the particular SNARE subtype (syntaxin, SNAP25, or VAMP), priming proteins (Munc18, Munc13, CAPS, complexin, or snapin), triggering proteins (synaptotagmins, Doc2, and various protein kinases), and the submembraneous cytomatrix, and they are the key to determining the kinetics of subsequent exocytosis. These distinct initial configurations will help us clarify the common SNARE assembly processes underlying exocytosis and membrane trafficking in eukaryotic cells.

scholarly journals TGN/EE SNARE protein SYP61 is ubiquitinated and required for carbon/nitrogen-nutrient responses in Arabidopsis

2020 ◽  
Author(s):  
Yoko Hasegawa ◽  
Thais Huarancca Reyes ◽  
Tomohiro Uemura ◽  
Akari Fujimaki ◽  
Yongming Luo ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Critical Role ◽  
Snare Protein ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Cargo Proteins ◽  
Golgi Network

AbstractUbiquitination is a post-translational modification with reversible attachment of the small protein ubiquitin, which is involved in numerous cellular processes including membrane trafficking. For example, ubiquitination of cargo proteins is known to regulate their subcellular dynamics, and plays important roles in plant growth and stress adaptation. However, the regulatory mechanism of the trafficking machinery components remains elusive. Here, we report Arabidopsis trans-Golgi network/early endosome (TGN/EE) localized soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein SYP61 as a novel ubiquitination target of a membrane localized ubiquitin ligase ATL31. SYP61 is a key component of membrane trafficking in Arabidopsis. SYP61 was ubiquitinated with K63-linked chain by ATL31 in vitro and in plants. The knockdown mutants of SYP61 were hypersensitive to the disrupted carbon (C)/nitrogen (N)-nutrient stress, suggesting its critical role in plant homeostasis in response to nutrients. We also found the ubiquitination status of SYP61 is affected by C/N-nutrient availability. These results provided possibility that ubiquitination of SNARE protein has important role in plant physiology.

scholarly journals Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion

Blood ◽  
2012 ◽  
Vol 120 (12) ◽  
pp. 2484-2492 ◽  
Author(s):  
Shaojing Ye ◽  
Zubair A. Karim ◽  
Rania Al Hawas ◽  
Jeffery E. Pessin ◽  
Alexandra H. Filipovich ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Critical Role ◽  
Snare Proteins ◽  
Mouse Strains ◽  
Double Knockout ◽  
Protein Receptor ◽  
Syntaxin 4 ◽  
Syntaxin 11 ◽  
Platelet Exocytosis ◽  
Platelet Secretion

Abstract The platelet release reaction plays a critical role in thrombosis and contributes to the events that follow hemostasis. Previous studies have shown that platelet secretion is mediated by Soluble NSF Attachment Protein Receptor (SNARE) proteins from granule and plasma membranes. The SNAREs form transmembrane complexes that mediate membrane fusion and granule cargo release. Although VAMP-8 (v-SNARE) and SNAP-23 (a t-SNARE class) are important for platelet secretion, the identity of the functional syntaxin (another t-SNARE class) has been controversial. Previous studies using anti-syntaxin Abs in permeabilized platelets have suggested roles for both syntaxin-2 and syntaxin-4. In the present study, we tested these conclusions using platelets from syntaxin-knockout mouse strains and from a Familial Hemophagocytic Lymphohistiocytosis type 4 (FHL4) patient. Platelets from syntaxin-2 and syntaxin-4 single- or double-knockout mice had no secretion defect. Platelets from a FHL4 patient deficient in syntaxin-11 had a robust defect in agonist-induced secretion although their morphology, activation, and cargo levels appeared normal. Semiquantitative Western blotting showed that syntaxin-11 is the more abundant syntaxin in both human and murine platelets. Coimmunoprecipitation experiments showed that syntaxin-11 can form SNARE complexes with both VAMP-8 and SNAP-23. The results of the present study indicate that syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet exocytosis.

scholarly journals SNARE Membrane Trafficking Dynamics In Vivo

1999 ◽  
Vol 144 (5) ◽  
pp. 869-881 ◽  
Author(s):  
Daniel S. Chao ◽  
Jesse C. Hay ◽  
Shawn Winnick ◽  
Rytis Prekeris ◽  
Judith Klumperman ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Fluorescent Proteins ◽  
Snare Proteins ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Er Exit Sites ◽  
Cytoplasmic Structures ◽  
Insight Into

The ER/Golgi soluble NSF attachment protein receptor (SNARE) membrin, rsec22b, and rbet1 are enriched in ∼1-μm cytoplasmic structures that lie very close to the ER. These appear to be ER exit sites since secretory cargo concentrates in and exits from these structures. rsec22b and rbet1 fused to fluorescent proteins are enriched at ∼1-μm ER exit sites that remained more or less stationary, but periodically emitted streaks of fluorescence that traveled generally in the direction of the Golgi complex. These exit sites were reused and subsequent tubules or streams of vesicles followed similar trajectories. Fluorescent membrin- enriched ∼1-μm peripheral structures were more mobile and appeared to translocate through the cytoplasm back and forth, between the periphery and the Golgi area. These mobile structures could serve to collect secretory cargo by fusing with ER-derived vesicles and ferrying the cargo to the Golgi. The post-Golgi SNAREs, syntaxin 6 and syntaxin 13, when fused to fluorescent proteins each displayed characteristic patterns of movement. However, syntaxin 13 was the only SNARE whose life cycle appeared to involve interactions with the plasma membrane. These studies reveal the in vivo spatiotemporal dynamics of SNARE proteins and provide new insight into their roles in membrane trafficking.

scholarly journals Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults

2021 ◽  
Vol 22 (4) ◽  
pp. 1926
Author(s):  
Julia Peñas-Martínez ◽  
María N. Barrachina ◽  
Ernesto José Cuenca-Zamora ◽  
Ginés Luengo-Gil ◽  
Susana Belén Bravo ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Critical Role ◽  
Snare Proteins ◽  
Term Neonates ◽  
Content Change ◽  
Protein Receptor ◽  
Transmission Electron ◽  
Health And Disease ◽  
Adult Plasma ◽  
Granule Secretion

Exosomes are extracellular vesicles that contain nucleic acids, lipids and metabolites, and play a critical role in health and disease as mediators of intercellular communication. The majority of extracellular vesicles in the blood are platelet-derived. Compared to adults, neonatal platelets are hyporeactive and show impaired granule release, associated with defects in Soluble N-ethylmaleimide-sensitive fusion Attachment protein REceptor (SNARE) proteins. Since these proteins participate in biogenesis of exosomes, we investigated the potential differences between newborn and adult plasma-derived exosomes. Plasma-derived exosomes were isolated by ultracentrifugation of umbilical cord blood from full-term neonates or peripheral blood from adults. Exosome characterization included size determination by transmission electron microscopy and quantitative proteomic analysis. Plasma-derived exosomes from neonates were significantly smaller and contained 65% less protein than those from adults. Remarkably, 131 proteins were found to be differentially expressed, 83 overexpressed and 48 underexpressed in neonatal (vs. adult) exosomes. Whereas the upregulated proteins in plasma exosomes from neonates are associated with platelet activation, coagulation and granule secretion, most of the underexpressed proteins are immunoglobulins. This is the first study showing that exosome size and content change with age. Our findings may contribute to elucidating the potential “developmental hemostatic mismatch risk” associated with transfusions containing plasma exosomes from adults.

C2C12 myocytes lack an insulin-responsive vesicular compartment despite dexamethasone-induced GLUT4 expression

2002 ◽  
Vol 283 (3) ◽  
pp. E514-E524 ◽  
Author(s):  
Lori L. Tortorella ◽  
Paul F. Pilch
Keyword(s):  
Glucose Transporter ◽  
Fold Increase ◽  
Snare Proteins ◽  
Vesicular Traffic ◽  
Glut4 Expression ◽  
Protein Receptor ◽  
Syntaxin 4 ◽  
Insulin Dependent ◽  
Glucose Transporter Glut4 ◽  
Vesicular Compartment

Insulin regulates the uptake of glucose into skeletal muscle and adipocytes by redistributing the tissue-specific glucose transporter GLUT4 from intracellular vesicles to the cell surface. To date, GLUT4 is the only protein involved in insulin-regulated vesicular traffic that has this tissue distribution, thus raising the possibility that its expression alone may allow formation of an insulin-responsive vesicular compartment. We show here that treatment of differentiating C2C12myoblasts with dexamethasone, acting via the glucocorticoid receptor, causes a ≥10-fold increase in GLUT4 expression but results in no significant change in insulin-stimulated glucose transport. Signaling from the insulin receptor to its target, Akt2, and expression of the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor, or SNARE, proteins syntaxin 4 and vesicle-associated membrane protein are normal in dexamethasone-treated C2C12 cells. However, these cells show no insulin-dependent trafficking of the insulin-responsive aminopeptidase or the transferrin receptor, respective markers for intracellular GLUT4-rich compartments and endosomes that are insulin responsive in mature muscle and adipose cells. Therefore, these data support the hypothesis that GLUT4 expression by itself is insufficient to establish an insulin-sensitive vesicular compartment.

scholarly journals The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein

2020 ◽  
Vol 295 (39) ◽  
pp. 13474-13487
Author(s):  
Marc R. Block ◽  
Molly Brunner ◽  
Théo Ziegelmeyer ◽  
Dominique Lallemand ◽  
Mylène Pezet ◽  
...  
Keyword(s):  
Late Endosome ◽  
Cell Periphery ◽  
Β1 Integrin ◽  
Nonreceptor Tyrosine Kinase ◽  
Cell Contractility ◽  
Late Endosomes ◽  
Important Regulator ◽  
Nuclear Shuttling ◽  
Endosomal System

Yes-associated protein (YAP) signaling has emerged as a crucial pathway in several normal and pathological processes. Although the main upstream effectors that regulate its activity have been extensively studied, the role of the endosomal system has been far less characterized. Here, we identified the late endosomal/lysosomal adaptor MAPK and mTOR activator (LAMTOR) complex as an important regulator of YAP signaling in a preosteoblast cell line. We found that p18/LAMTOR1-mediated peripheral positioning of late endosomes allows delivery of SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) to the plasma membrane and promotes activation of an SRC-dependent signaling cascade that controls YAP nuclear shuttling. Moreover, β1 integrin engagement and mechano-sensitive cues, such as external stiffness and related cell contractility, controlled LAMTOR targeting to the cell periphery and thereby late endosome recycling and had a major impact on YAP signaling. Our findings identify the late endosome recycling pathway as a key mechanism that controls YAP activity and explains YAP mechano-sensitivity.

scholarly journals Non-autophagy role of Atg5 and NBR1 in unconventional secretion of IL-12 prevents gut dysbiosis and inflammation

2020 ◽  
Author(s):  
Seth D. Merkley ◽  
Samuel M. Goodfellow ◽  
Yan Guo ◽  
Zoe E.R. Wilton ◽  
Janie R. Byrum ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Myeloid Cells ◽  
Late Endosome ◽  
Gut Dysbiosis ◽  
Cargo Receptor ◽  
Unconventional Secretion ◽  
Genetic Deletion

ABSTRACTIntestinal myeloid cells play a critical role in balancing intestinal homeostasis and inflammation. Here, we report that expression of the autophagy related 5 (Atg5) protein in myeloid cells prevents dysbiosis and excessive intestinal inflammation by limiting IL-12 production. Mice with a selective genetic deletion of Atg5 in myeloid cells (Atg5ΔMye) showed signs of dysbiosis prior to colitis and exhibited severe intestinal inflammation upon colitis induction that was characterized by increased IFNγ production. This increase in IFNγ was due to excess IL-12 secretion from Atg5-deficient myeloid cells. Atg5 functions to limit IL-12 secretion through modulation of late endosome (LE) acidity. Additionally, the autophagy cargo receptor NBR1, which accumulates in Atg5-deficient cells, played a role by delivering IL-12 to LE. Restoration of the intestinal microbiota and alleviation of intestinal inflammation was achieved by genetic deletion of IL-12 in Atg5ΔMye mice. In summary, Atg5 expression in intestinal myeloid cells acts as an anti-inflammatory brake to regulate IL-12 thus preventing dysbiosis and uncontrolled IFNγ-driven intestinal inflammation.

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