SNARE Status Regulates Tether Recruitment and Function in Homotypic COPII Vesicle Fusion

Normal neural development is essential for the formation of neuronal networks and brain function. Cutaneous T cell lymphoma-associated antigen 5 (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the secretion of proteins. However, its roles in the transport of nonsecretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is important for brain development and function. Conditional knockout ofcTAGE5/MEA6in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, spine formation and maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects in COPII vesicle formation and transport from the endoplasmic reticulum to the Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines but also the signaling pathways required for neuronal development. Because mutations in cTAGE5/MEA6 have been found in patients with Fahr’s disease, our study potentially also provides insight into the pathogenesis of this disorder.

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Faculty Opinions recommendation of Reconstitution of COPII vesicle fusion to generate a pre-Golgi intermediate compartment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023178.266683 ◽

2005 ◽

Author(s):

Howard Riezman

Keyword(s):

Vesicle Fusion ◽

Copii Vesicle ◽

Intermediate Compartment

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Vesicular Calcium Regulates Coat Retention, Fusogenicity, and Size of Pre-Golgi Intermediates

Molecular Biology of the Cell ◽

10.1091/mbc.e09-10-0914 ◽

2010 ◽

Vol 21 (6) ◽

pp. 1033-1046 ◽

Cited By ~ 40

Author(s):

Marvin Bentley ◽

Deborah C. Nycz ◽

Ashwini Joglekar ◽

Ismene Fertschai ◽

Roland Malli ◽

...

Keyword(s):

Secretory Pathway ◽

Rat Kidney ◽

Cyclopiazonic Acid ◽

Early Secretory Pathway ◽

Shell Protein ◽

Ef Hand ◽

Copii Vesicle ◽

Normal Rat ◽

And Function

The significance and extent of Ca2+ regulation of the biosynthetic secretory pathway have been difficult to establish, and our knowledge of regulatory relationships integrating Ca2+ with vesicle coats and function is rudimentary. Here, we investigated potential roles and mechanisms of luminal Ca2+ in the early secretory pathway. Specific depletion of luminal Ca2+ in living normal rat kidney cells using cyclopiazonic acid (CPA) resulted in the extreme expansion of vesicular tubular cluster (VTC) elements. Consistent with this, a suppressive role for vesicle-associated Ca2+ in COPII vesicle homotypic fusion was demonstrated in vitro using Ca2+ chelators. The EF-hand–containing protein apoptosis-linked gene 2 (ALG-2), previously implicated in the stabilization of sec31 at endoplasmic reticulum exit sites, inhibited COPII vesicle fusion in a Ca2+-requiring manner, suggesting that ALG-2 may be a sensor for the effects of vesicular Ca2+ on homotypic fusion. Immunoisolation established that Ca2+ chelation inhibits and ALG-2 specifically favors residual retention of the COPII outer shell protein sec31 on pre-Golgi fusion intermediates. We conclude that vesicle-associated Ca2+, acting through ALG-2, favors the retention of residual coat molecules that seem to suppress membrane fusion. We propose that in cells, these Ca2+-dependent mechanisms temporally regulate COPII vesicle interactions, VTC biogenesis, cargo sorting, and VTC maturation.

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Room for Two: The Synaptophysin/Synaptobrevin Complex

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2021.740318 ◽

2021 ◽

Vol 13 ◽

Author(s):

Dustin N. White ◽

Michael H. B. Stowell

Keyword(s):

Transmembrane Protein ◽

Vesicle Fusion ◽

Snare Complex ◽

Synaptic Proteins ◽

Phospholipid Bilayer ◽

Synaptic Membrane ◽

Neuronal Communication ◽

Form And Function ◽

Protein Receptors ◽

And Function

Synaptic vesicle release is regulated by upwards of 30 proteins at the fusion complex alone, but disruptions in any one of these components can have devastating consequences for neuronal communication. Aberrant molecular responses to calcium signaling at the pre-synaptic terminal dramatically affect vesicle trafficking, docking, fusion, and release. At the organismal level, this is reflected in disorders such as epilepsy, depression, and neurodegeneration. Among the myriad pre-synaptic proteins, perhaps the most functionally mysterious is synaptophysin (SYP). On its own, this vesicular transmembrane protein has been proposed to function as a calcium sensor, a cholesterol-binding protein, and to form ion channels across the phospholipid bilayer. The downstream effects of these functions are largely unknown. The physiological relevance of SYP is readily apparent in its interaction with synaptobrevin (VAMP2), an integral element of the neuronal SNARE complex. SNAREs, soluble NSF attachment protein receptors, comprise a family of proteins essential for vesicle fusion. The complex formed by SYP and VAMP2 is thought to be involved in both trafficking to the pre-synaptic membrane as well as regulation of SNARE complex formation. Recent structural observations specifically implicate the SYP/VAMP2 complex in anchoring the SNARE assembly at the pre-synaptic membrane prior to vesicle fusion. Thus, the SYP/VAMP2 complex appears vital to the form and function of neuronal exocytotic machinery.

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Faculty Opinions recommendation of Reconstitution of COPII vesicle fusion to generate a pre-Golgi intermediate compartment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023178.269638 ◽

2005 ◽

Author(s):

Vojo Deretic

Keyword(s):

Vesicle Fusion ◽

Copii Vesicle ◽

Intermediate Compartment

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Faculty Opinions recommendation of Reconstitution of COPII vesicle fusion to generate a pre-Golgi intermediate compartment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023178.292762 ◽

2005 ◽

Author(s):

Craig Roy

Keyword(s):

Vesicle Fusion ◽

Copii Vesicle ◽

Intermediate Compartment

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Faculty Opinions recommendation of Reconstitution of COPII vesicle fusion to generate a pre-Golgi intermediate compartment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023178.283707 ◽

2005 ◽

Author(s):

Sebastian Springer

Keyword(s):

Vesicle Fusion ◽

Copii Vesicle ◽

Intermediate Compartment

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Conformation of Ribosomes from Escherichia Coli

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051062 ◽

1974 ◽

Vol 32 ◽

pp. 210-211

Author(s):

M. Boublik ◽

W. Hellmann ◽

F. Jenkins

Keyword(s):

Binding Sites ◽

Ribosomal Proteins ◽

Fluorescent Dyes ◽

Protein Biosynthesis ◽

Three Dimensional ◽

Spatial Arrangement ◽

Dimensional Structure ◽

Complete Understanding ◽

And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

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