Golgi Glycosylation and Human Inherited Diseases

Freeze, Hudson H.; Ng, Bobby G.

doi:10.1101/cshperspect.a005371

Cited by 72 publications

(74 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to containing a large number of enzymes that are responsible for catalyzing protein and lipid modifications, the Golgi houses many proteins that are involved in packaging, tethering and transporting secretory vesicles (Linstedt and Hauri, 1993;Munro, 2011;Puthenveedu and Linstedt, 2001;Short et al, 2005;Zhong, 2011). Dozens of human developmental disorders and diseases have been associated with mutations in Golgi-associated proteins (Freeze and Ng, 2011;Smits et al, 2010). Remarkably, several mutations in genes encoding vesicle transport proteins cause craniofacial and skeletal disorders with distinct phenotypes (Follit et al, 2008;Freeze and Ng, 2011;Kim et al, 2012;Smits et al, 2010), which highlights the importance of understanding Golgimediated cell biological processes in the context of development (Freeze and Ng, 2011;Kim et al, 2012;Smits et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

View full text Add to dashboard Cite

Cleft palate is a common major birth defect for which currently known causes account for less than 30% of pathology in humans. In this study, we carried out mutagenesis screening in mice to identify new regulators of palatogenesis. Through genetic linkage mapping and whole exome sequencing, we identified a loss-of-function mutation in the Golgb1 gene that co-segregated with cleft palate in a new mutant mouse line. Golgb1 encodes a ubiquitously expressed large coiled-coil protein, known as giantin, that is localized at the Golgi membrane. Using CRISPR/Cas9-mediated genome editing, we generated and analyzed developmental defects in mice carrying additional Golgb1 loss-of-function mutations, which validated a critical requirement for Golgb1 in palate development. Through maxillary explant culture assays, we demonstrate that the Golgb1 mutant embryos have intrinsic defects in palatal shelf elevation. Just prior to the developmental stage of palatal shelf elevation in the wildtype littermates, Golgb1 mutant embryos exhibit increased cell density, reduced hyaluronan accumulation, and impaired protein glycosylation in the palatal mesenchyme. Together, these results demonstrate that, although it is a ubiquitously expressed Golgi-associated protein, Golgb1 has specific functions in protein glycosylation and tissue morphogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Defects in individual COG subunits can lead to the aberrant distribution of glycosylation enzymes within the Golgi and thereby to severe genetic diseases known as congenital disorders of glycosylation (CDGs) (17,18). The first CDG to be attributed to a COG complex defect was traced to a mutation in the COG7 gene, with infants homozygous for the mutation dying a few weeks after birth (19).…”

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.

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

“…Beyond kinases, Hsc70 and its J-domain-containing cochaperones auxilin and cyclin G-associated kinase (GAK) (McMahon and Boucrot 2011) are central to the function of the clathrin coat by promoting clathrin cage disassembly and recycling (Schmid and Rothman 1985;Bocking et al 2011;Rothnie et al 2011). Moreover, genetic evidence suggests a role for Hsp90 in the assembly and function of the tether "congenital disorders of glycosylation" (COG) TRaCKS components, which regulate the compartmentalization of Golgi glycosylation biology (see below) (Banfield 2011; Freeze and Ng 2011;Geller et al 2012;Rosnoblet et al 2012). Finally, increasing evidence implicates a general role for Hsc/p70 and Hsp90 in vesicle tethering and fusion, mediated by sequential RAB GTPase and SNARE TRaCKS found in the Golgi (Chen and Balch 2006) and at the synapse (Sakisaka et al 2002;Sharma et al 2012b).…”

Section: Role Of Ups In Cargo-specific Tracks Biologymentioning

confidence: 99%

“…4B) (Pokrovskaya et al 2011;Reynders et al 2011). COG complex subunits, when mutated, result in specific glycosylation defective diseases (Freeze and Ng 2011;Rosnoblet et al 2012), yet do not perturb the general flow of cargo. The ability of GT components to self-organize relative to other cargo was recognized by Warren and colleagues as "kin recognition" (Nilsson et al 1993)-illustrating the principle of affinity/avidity-based construction of a specific Golgi mosaic (Fig.…”

Section: Tpn Biology and Anfinsen Compartmentsmentioning

confidence: 99%

“…Trafficking components (Allan et al 2000;Barrowman et al 2010;Koulov et al 2010;Miller and Barlowe 2010;Balch et al 2011;Lord et al 2011;Coppinger et al 2012;Zanetti et al 2012) that manage compartment structure and function to provide special environments to manipulate the protein fold are largely cytosolic proteins and fall into three categories: the coat protein complexes and their adaptors including the COPII, COPI, clathrin, adaptor proteins (APs) (Stagg et al 2007;Dancourt and Barlowe 2010;Routledge et al 2010;Lord et al 2011;Popoff et al 2011;Weinberg and Drubin 2012;Zanetti et al 2012); the tether complexes including PGGM ( p115-Grasp-GM130), ESCRT, COG, GOLGINs, and TRAPP complexes, among others, that serve as scaffolds to transiently link compartments in response to the activity of coat and fusion components (Allan et al 2000;Barrowman et al 2010;Nakamura 2010;Freeze and Ng 2011;Henne et al 2011;Munro 2011a); and the fusion system that consists of the N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors (SNARE) components and multiple supporting SNARE assembly and disassembly factors including AAA ATPase NSF (Sudhof and Rothman 2009;Wickner 2010). We now appreciate that these integrated coat, tether, and fusion (CTF) scaffolds, although evolutionarily conserved (Gurkan et al 2007;Dacks et al 2009;Brighouse et al 2010;Klute et al 2011;Elias et al 2012), are often unique and/or highly specialized for each cell type .…”

Section: Uprmentioning

confidence: 99%

See 1 more Smart Citation

Expanding Proteostasis by Membrane Trafficking Networks

Hutt

Balch

2013

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

The folding biology common to all three kingdoms of life (Archaea, Bacteria, and Eukarya) is proteostasis. The proteostasis network (PN) functions as a "cloud" to generate, protect, and degrade the proteome. Whereas microbes (Bacteria, Archaea) have a single compartment, Eukarya have numerous subcellular compartments. We examine evidence that Eukarya compartments use coat, tether, and fusion (CTF) membrane trafficking components to form an evolutionarily advanced arm of the PN that we refer to as the "trafficking PN" (TPN). We suggest that the TPN builds compartments by generating a mosaic of integrated cargo-specific trafficking signatures (TRaCKS). TRaCKS control the temporal and spatial features of protein-folding biology based on the Anfinsen principle that the local environment plays a critical role in managing protein structure. TPN-generated endomembrane compartments apply a "quinary" level of structural control to modify the secondary, tertiary, and quaternary structures defined by the primary polypeptide-chain sequence. The development of Anfinsen compartments provides a unifying foundation for understanding the purpose of endomembrane biology and its capacity to drive extant Eukarya function and diversity.

show abstract

Golgi Glycosylation and Human Inherited Diseases

Cited by 72 publications

References 168 publications

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

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

Expanding Proteostasis by Membrane Trafficking Networks

Contact Info

Product

Resources

About