Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Paczkowski, Jon E.; Richardson, Brian C.; Fromme, J. Christopher

doi:10.1016/j.tcb.2015.02.005

Cited by 64 publications

(77 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The AP complexes involved in sorting during the formation of clathrin-coated vesicles are generally recruited to membranes by binding to the cytoplasmic tails of integral transmembrane proteins. 36 How then does VWF, a protein with no transmembrane domains, recruit AP-1? To date, there is no identified abundant integral membrane VWF-binding protein to recruit AP-1.…”

Section: Discussionmentioning

confidence: 99%

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells

Silva

Cutler

2016

Blood

View full text Add to dashboard Cite

Key Points• The 3 endothelial secretory pathways-constitutive, basal, and regulated-release VWF in different multimeric states.• Apical-and basolaterallyreleased VWF follow different secretory pathways, thus releasing differentially multimerized protein.The von Willebrand factor (VWF) synthesized and secreted by endothelial cells is central to hemostasis and thrombosis, providing a multifunctional adhesive platform that brings together components needed for these processes. VWF secretion can occur from both apical and basolateral sides of endothelial cells, and from constitutive, basal, and regulated secretory pathways, the latter two via Weibel-Palade bodies (WPB). Although the amount and structure of VWF is crucial to its function, the extent of VWF release, multimerization, and polarity of the 3 secretory pathways have only been addressed separately, and with conflicting results. We set out to clarify these relationships using polarized human umbilical vein endothelial cells (HUVECs) grown on Transwell membranes. We found that regulated secretion of ultra-large (UL)-molecular-weight VWF predominantly occurred apically, consistent with a role in localized platelet capture in the vessel lumen. We found that constitutive secretion of low-molecular-weight (LMW) VWF is targeted basolaterally, toward the subendothelial matrix, using the adaptor protein complex 1 (AP-1), where it may provide the bulk of collagen-bound subendothelial VWF. We also found that basally-secreted VWF is composed of UL-VWF, released continuously from WPBs in the absence of stimuli, and occurs predominantly apically, suggesting this could be the main source of circulating plasma VWF. Together, we provide a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive, basal, and regulated pathways in polarized HUVECs, and have established a new role for AP-1 in the basolateral constitutive secretion of VWF. (Blood. 2016;128(2):277-285)

show abstract

Section: Discussionmentioning

confidence: 99%

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells

Silva

Cutler

2016

Blood

View full text Add to dashboard Cite

show abstract

“…To integrate data from different organisms, Day, Staehelin and Glick recently proposed that three fundamentally different classes of compartments can be distinguished based on the pathways operating to and from them (Day et al 2013, Papanikou andGlick 2014): (i) the cisternal assembly stage, during which cisternae accept COPII biosynthetic traffic from the ER and deliver back to it COPI-coated vesicles, recycling trafficking components and ER resident proteins, (ii) the carbohydrate synthesis stage, where intra-Golgi transport takes place via COPI-dependent traffic exchange and (iii) the carrier formation stage, during which cisternae receive endosome traffic and form clathrin-coated carriers bound to the endosomes and secretory carriers bound to the plasma membrane (Paczkowski et al 2015).…”

Section: Golgi Functional Entities: the Golgi As Central Hub Of Intramentioning

confidence: 99%

The Golgi apparatus: insights from filamentous fungi

Pantazopoulou

2016

Mycologia

View full text Add to dashboard Cite

Cargo passage through the Golgi, albeit an undoubtedly essential cellular function, is a mechanistically unresolved and much debated process. Although the main molecular players are conserved, diversification of the Golgi among different eukaryotic lineages is providing us with tools to resolve standing controversies. During the past decade the Golgi apparatus of model filamentous fungi, mainly Aspergillus nidulans, has been intensively studied. Here an overview of the most important findings in the field is provided. Golgi architecture and dynamics, as well as the novel cell biology tools that were developed in filamentous fungi in these studies, are addressed. An emphasis is placed on the central role the Golgi has as a crossroads in the endocytic and secretory-traffic pathways in hyphae. Finally the major advances that the A. nidulans Golgi biology has yielded so far regarding our understanding of key Golgi regulators, such as the Rab GTPases RabC Rab6 and RabE Rab11 , the oligomeric transport protein particle, TRAPPII, and the Golgi guanine nucleotide exchange factors of Arf1, GeaA GBF1/Gea1 and HypB BIG/Sec7 , are highlighted.

show abstract

“…Clathrin adaptors serve as central hubs in the physical and functional networks that drive ccv biogenesis. In particular, adaptors anchor the clathrin coat scaffold to the membrane, collect cargo, and recruit accessory factors that contribute to multiple steps in vesicle formation, including membrane invagination and vesicle release (1)(2)(3).…”

mentioning

confidence: 99%

Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the trans -Golgi network

Daboussi

Costaguta

Ghukasyan

et al. 2017

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

View full text Add to dashboard Cite

Phosphoinositides serve as key membrane determinants for assembly of clathrin coat proteins that drive formation of clathrin-coated vesicles. At the trans-Golgi network (TGN), phosphatidylinositol 4-phosphate (PtdIns4P) plays important roles in recruitment of two major clathrin adaptors, Gga (Golgi-localized, gamma-adaptin ear homology, Arf-binding) proteins and the AP-1 (assembly protein-1) complex. The molecular mechanisms that mediate localization of phosphatidylinositol kinases responsible for synthesis of PtdIns4P at the TGN are not well characterized. We identify two motifs in the yeast phosphatidylinositol 4-kinase, Pik1, which are required for binding to the VHS domain of Gga2. Mutations in these motifs that inhibit Gga2-VHS binding resulted in reduced Pik1 localization and delayed accumulation of PtdIns4P and recruitment of AP-1 to the TGN. The Pik1 homolog in mammals, PI4KIIIβ, interacted preferentially with the VHS domain of GGA2 compared with VHS domains of GGA1 and GGA3. Depletion of GGA2, but not GGA1 or GGA3, specifically affected PI4KIIIβ localization. These results reveal a conserved role for Gga proteins in regulating phosphatidylinositol 4-kinase function at the TGN.clathrin | Gga adaptors | phosphatidylinositol 4-kinase | phosphatidylinositol 4-phosphate | trans-Golgi network

show abstract

Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Cited by 64 publications

References 111 publications

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells

The Golgi apparatus: insights from filamentous fungi

Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the trans -Golgi network

Contact Info

Product

Resources

About