Tethering Factors as Organizers of Intracellular Vesicular Traffic

Yu, I-Mei; Hughson, Frederick M.

doi:10.1146/annurev.cellbio.042308.113327

Cited by 302 publications

(404 citation statements)

References 139 publications

Supporting

Mentioning

396

Contrasting

Unclassified

Order By: Relevance

“…In current working models, anterograde-directed COPI vesicles are targeted to preceding Golgi compartments by the conserved oligomeric Golgi (COG) complex, a large multisubunit tethering complex identified through a combination of genetic and biochemical approaches (Miller and Ungar 2012). COG consists of eight subunits and belongs to the larger CATCHR (complex associated with tethering containing helical rods) family of tethering factors that includes the exocyst and GARP complexes (Yu and Hughson 2010). In intra-Golgi retrograde transport, the COG complex appears to operate as a tethering and fusion hub with multiple interactions that link COG to the g-COPI subunit, to Ypt1 and to Golgi SNARE proteins (Suvorova et al 2002).…”

Section: Transport Through the Golgi Complexmentioning

confidence: 99%

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

2013

View full text Add to dashboard Cite

The secretory pathway is responsible for the synthesis, folding, and delivery of a diverse array of cellular proteins. Secretory protein synthesis begins in the endoplasmic reticulum (ER), which is charged with the tasks of correctly integrating nascent proteins and ensuring correct post-translational modification and folding. Once ready for forward traffic, proteins are captured into ER-derived transport vesicles that form through the action of the COPII coat. COPII-coated vesicles are delivered to the early Golgi via distinct tethering and fusion machineries. Escaped ER residents and other cycling transport machinery components are returned to the ER via COPI-coated vesicles, which undergo similar tethering and fusion reactions. Ultimately, organelle structure, function, and cell homeostasis are maintained by modulating protein and lipid flux through the early secretory pathway. In the last decade, structural and mechanistic studies have added greatly to the strong foundation of yeast genetics on which this field was built. Here we discuss the key players that mediate secretory protein biogenesis and trafficking, highlighting recent advances that have deepened our understanding of the complexity of this conserved and essential process. TABLE OF CONTENTS Abstract 383Introduction 384

show abstract

Section: Transport Through the Golgi Complexmentioning

confidence: 99%

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

2013

View full text Add to dashboard Cite

show abstract

“…The remaining subunits are predicted to have similar structures (43). This structural characterization places the exocyst into the conserved CATCHR (complexes associated with tethering containing helical rods) family of tethering complexes (2).…”

mentioning

confidence: 91%

“…These trafficking processes must be tightly regulated to ensure spatial and temporal delivery of vesicles to their cellular destination. Many conserved protein families are essential for trafficking, including the SNARE proteins that provide the impetus for membrane fusion (1) and the multisubunit tethering complexes (MTCs) 2 proposed to tether vesicles to sites of fusion (2,3). However, the details of these processes are still poorly understood at the mechanistic level.…”

mentioning

confidence: 99%

The Exocyst Subunit Sec6 Interacts with Assembled Exocytic SNARE Complexes

Dubuke

Maniatis

Shaffer

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Sec6 has been reported to inhibit SNARE complex assembly, in contrast to other tethering complexes. Results: Sec6 does not inhibit SNARE assembly. Rather, it binds assembled SNARE complexes. Disrupting this interaction results in growth defects in yeast. Conclusion: This interaction is important for a functional exocytic pathway. Significance: The exocyst is likely to have mechanisms of SNARE regulation comparable with other multisubunit tethering complexes.

show abstract

“…Among the most complex and least well-characterized components of this machinery are the multisubunit tethering complexes (MTCs) (2). MTCs are thought to mediate the initial attachment (or tethering) between a trafficking vesicle and its target membrane through a constellation of interactions (3,4).…”

mentioning

confidence: 99%

Cog5–Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex

Pokrovskaya

Climer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The conserved oligomeric Golgi (COG) complex is required, along with SNARE and Sec1/Munc18 (SM) proteins, for vesicle docking and fusion at the Golgi. COG, like other multisubunit tethering complexes (MTCs), is thought to function as a scaffold and/or chaperone to direct the assembly of productive SNARE complexes at the sites of membrane fusion. Reflecting this essential role, mutations in the COG complex can cause congenital disorders of glycosylation. A deeper understanding of COG function and dysfunction will likely depend on elucidating its molecular structure. Despite some progress toward this goal, including EM studies of COG lobe A (subunits 1-4) and higher-resolution structures of portions of Cog2 and Cog4, the structures of COG's eight subunits and the principles governing their assembly are mostly unknown. Here, we report the crystal structure of a complex between two lobe B subunits, Cog5 and Cog7. The structure reveals that Cog5 is a member of the complexes associated with tethering containing helical rods (CATCHR) fold family, with homology to subunits of other MTCs including the Dsl1, exocyst, and Golgi-associated retrograde protein (GARP) complexes. The Cog5-Cog7 interaction is analyzed in relation to the Dsl1 complex, the only other CATCHR-family MTC for which subunit interactions have been characterized in detail. Biochemical and functional studies validate the physiological relevance of the observed Cog5-Cog7 interface, indicate that it is conserved from yeast to humans, and demonstrate that its disruption in human cells causes defects in trafficking and glycosylation.I n eukaryotes, the transport of proteins and lipids among intracellular compartments is mediated by vesicular and tubular carriers under the direction of an elaborate protein machinery (1). Among the most complex and least well-characterized components of this machinery are the multisubunit tethering complexes (MTCs) (2). MTCs are thought to mediate the initial attachment (or tethering) between a trafficking vesicle and its target membrane through a constellation of interactions (3, 4). These may include binding of the MTC to activated Rab GTPases, coiled-coil proteins such as Golgins, vesicle coat proteins, SNAREs, Sec1/ Munc18 (SM) proteins, and/or membrane lipids. Elucidating the 3D structures of MTCs represents an important step toward a better understanding of their molecular functions.Four of the known MTCs-termed complexes associated with tethering containing helical rods (CATCHR) or quatrefoil complexes (2, 5)-contain subunits whose shared 3D structure implies a single evolutionary progenitor (6-16). These CATCHR-family MTCs include the Dsl1, Golgi-associated retrograde protein (GARP), exocyst, and conserved oligomeric Golgi (COG) complexes, and they contain three, four, eight, and eight subunits, respectively. Although X-ray or NMR structures have been reported for 14 of these 23 subunits, only one of the structures contains the full-length polypeptide (14). Perhaps more critically, only two subunit interactions-both wit...

show abstract

Tethering Factors as Organizers of Intracellular Vesicular Traffic

Cited by 302 publications

References 139 publications

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

The Exocyst Subunit Sec6 Interacts with Assembled Exocytic SNARE Complexes

Cog5–Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex

Contact Info

Product

Resources

About