scholarly journals Getting Sugar Coating Right! The Role of the Golgi Trafficking Machinery in Glycosylation

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3275
Author(s):  
Zinia D’Souza ◽  
Farhana Taher Sumya ◽  
Amrita Khakurel ◽  
Vladimir Lupashin
Keyword(s):  
Ion Channels ◽  
Secretory Pathway ◽  
Small Gtpases ◽  
Vesicular Trafficking ◽  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation ◽  
Sugar Transporters ◽  
Vesicle Tethering ◽  
Independent Process

The Golgi is the central organelle of the secretory pathway and it houses the majority of the glycosylation machinery, which includes glycosylation enzymes and sugar transporters. Correct compartmentalization of the glycosylation machinery is achieved by retrograde vesicular trafficking as the secretory cargo moves forward by cisternal maturation. The vesicular trafficking machinery which includes vesicular coats, small GTPases, tethers and SNAREs, play a major role in coordinating the Golgi trafficking thereby achieving Golgi homeostasis. Glycosylation is a template-independent process, so its fidelity heavily relies on appropriate localization of the glycosylation machinery and Golgi homeostasis. Mutations in the glycosylation enzymes, sugar transporters, Golgi ion channels and several vesicle tethering factors cause congenital disorders of glycosylation (CDG) which encompass a group of multisystem disorders with varying severities. Here, we focus on the Golgi vesicle tethering and fusion machinery, namely, multisubunit tethering complexes and SNAREs and their role in Golgi trafficking and glycosylation. This review is a comprehensive summary of all the identified CDG causing mutations of the Golgi trafficking machinery in humans.

GRASP55: A Multifunctional Protein

2020 ◽  
Vol 21 (6) ◽  
pp. 544-552 ◽  
Author(s):  
Hongrong Wu ◽  
Tianjiao Li ◽  
Jianfeng Zhao
Keyword(s):  
Crucial Role ◽  
Protein Modification ◽  
Secretory Pathway ◽  
Cell Activity ◽  
Vesicular Trafficking ◽  
Multifunctional Protein ◽  
Autophagosome Maturation

GRASP55 was first found as Golgi cisternae stacking protein. Due to the crucial role of Golgi in vesicular trafficking and protein modification, GRASP55 was found to function in these two aspects. Further investigation revealed that GRASP55 also participates in the unconventional secretory pathway under stress. Moreover, GRASP55 is involved in autophagy initiation and autophagosome maturation, as well as cell activity.

scholarly journals Shared and specific functions of Arfs 1–5 at the Golgi revealed by systematic knockouts

2021 ◽  
Author(s):  
Mirjam Pennauer ◽  
Katarzyna Buczak ◽  
Cristina Prescianotto-Baschong ◽  
Martin Spiess
Keyword(s):  
Cell Lines ◽  
Secretory Pathway ◽  
Small Gtpases ◽  
Class I ◽  
Growth Defect ◽  
Human Class ◽  
Slight Growth ◽  
Dependent Processes

AbstractThe ADP-ribosylation factors (Arfs) are small GTPases regulating membrane traffic in the secretory pathway. They are closely related and appear to have overlapping functions, regulators, and effectors. The functional specificity of individual Arfs and the extent of redundancy in vivo are still largely unknown. We addressed these questions by CRISPR/Cas9-mediated genomic deletion of the human class I (Arfs 1 and 3) and class II (Arfs 4 and 5) Arfs, either individually or in combination. Cells lacking individual Arfs or certain combinations were viable with only a slight growth defect when lacking Arf1 or Arf4. However, Arf1 and 4, and Arf4 and 5 could not be deleted simultaneously. Hence, class I Arfs are not essential and Arf4 alone was found to be sufficient for cell viability. Remarkably, two single knockouts produced specific and distinct phenotypes. Upon deletion of Arf1, the Golgi complex was enlarged and recruitment of vesicle coats decreased, confirming a major role of Arf1 in coat formation at the Golgi. Cell lines deleted for Arf4 exhibited secretion of ER resident proteins, indicating a specific defect in coatomer-dependent ER protein retrieval by the KDEL receptors. The knockout cell lines will be a useful tool to study other Arf-dependent processes.

scholarly journals Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning

2021 ◽  
Author(s):  
Hannes E Bülow ◽  
Maisha Rahman ◽  
Nelson J. Ramirez-Suarez ◽  
Carlos A Diaz-Balzac
Keyword(s):  
Nervous System ◽  
Molecular Diversity ◽  
Secretory Pathway ◽  
Extracellular Proteins ◽  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation ◽  
Glycosylation Sites ◽  
Key Enzyme ◽  
High Mannose ◽  
Adhesion Complex

N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate the activity of an extracellular protein complex involved in patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans regulates the activity of the Menorin adhesion complex without obviously affecting protein stability and localization of its components. AMAN-2 functions cell-autonomously to ensure decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with high-mannose/hybrid N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate the DMA-1/LRR-TM receptor, which together with three other extracellular proteins forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.

scholarly journals Shared and specific functions of Arfs 1–5 at the Golgi revealed by systematic knockouts

2021 ◽  
Vol 221 (1) ◽  
Author(s):  
Mirjam Pennauer ◽  
Katarzyna Buczak ◽  
Cristina Prescianotto-Baschong ◽  
Martin Spiess
Keyword(s):  
Cell Lines ◽  
Secretory Pathway ◽  
Small Gtpases ◽  
Class I ◽  
Human Class ◽  
Functional Specificity ◽  
Growth Defects ◽  
Slight Growth ◽  
Dependent Processes

ADP-ribosylation factors (Arfs) are small GTPases regulating membrane traffic in the secretory pathway. They are closely related and appear to have overlapping functions, regulators, and effectors. The functional specificity of individual Arfs and the extent of redundancy are still largely unknown. We addressed these questions by CRISPR/Cas9-mediated genomic deletion of the human class I (Arf1/3) and class II (Arf4/5) Arfs, either individually or in combination. Most knockout cell lines were viable with slight growth defects only when lacking Arf1 or Arf4. However, Arf1+4 and Arf4+5 could not be deleted simultaneously. Class I Arfs are nonessential, and Arf4 alone is sufficient for viability. Upon Arf1 deletion, the Golgi was enlarged, and recruitment of vesicle coats decreased, confirming a major role of Arf1 in vesicle formation at the Golgi. Knockout of Arf4 caused secretion of ER-resident proteins, indicating specific defects in coatomer-dependent ER protein retrieval by KDEL receptors. The knockout cell lines will be useful tools to study other Arf-dependent processes.

Acid-Sensing Ion Channels

2020 ◽  
Author(s):  
Stefan Gründer
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Excitatory Synapses ◽  
Detailed Characterization ◽  
High Affinity ◽  
Acid Sensing Ion Channels ◽  
Long Time ◽  
Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

scholarly journals Congenital disorders of glycosylation in children - histopathological and ultrastructural changes in the liver

2021 ◽  
Author(s):  
Patryk Lipiński ◽  
Joanna Cielecka-Kuszyk ◽  
Elżbieta Czarnowska ◽  
Anna Bogdańska ◽  
Piotr Socha ◽  
...  
Keyword(s):  
Ultrastructural Changes ◽  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation
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