A quantitative study of the Golgi retention of glycosyltransferases

How Golgi glycosyltransferases and glycosidases (hereafter glycosyltransferases) localize to the Golgi is still unclear. Here, we first investigated the post-Golgi trafficking of glycosyltransferases. We found that glycosyltransferases can escape the Golgi to the plasma membrane, where they are subsequently endocytosed to the endolysosome. Post-Golgi glycosyltransferases are probably degraded by the ectodomain shedding. We discovered that most glycosyltransferases are not retrieved from post-Golgi sites, indicating that retention but not retrieval should be the primary mechanism for their Golgi localization. We proposed to use the Golgi residence time to quantitatively and systematically study Golgi retention of glycosyltransferases. Various swapping chimeras between ST6GAL1 and either transferrin receptor or tumor necrosis factor α quantitatively revealed the contributions of three regions of ST6GAL1, namely the N-terminal cytosolic tail, transmembrane domain, and ectodomain, to Golgi retention. We found that each of the three regions is sufficient to produce retention in an additive manner. The N-terminal cytosolic tail length negatively affects the Golgi retention of ST6GAL1, similar to the effect of the transmembrane domain. Therefore, the long N-terminal cytosolic tail and transmembrane domain can be a Golgi export signal for transmembrane secretory cargos.

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A quantitative study of the Golgi retention of glycosyltransferases

10.1101/2021.02.15.431224 ◽

2021 ◽

Author(s):

Xiuping Sun ◽

Bing Chen ◽

Zhiwei Song ◽

Lei Lu

Keyword(s):

Plasma Membrane ◽

Transferrin Receptor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Transmembrane Domain ◽

Tail Length ◽

Golgi Retention ◽

Factor Α ◽

Export Signal ◽

Necrosis Factor

ABSTRACTHow Golgi glycosyltransferases and glycosidases (hereafter glycosyltransferases) localize to the Golgi is still unclear. Here, we first investigated the post-Golgi trafficking of glycosyltransferases. We found that glycosyltransferases can escape the Golgi to the plasma membrane, where they are subsequently endocytosed to the endolysosome. Post-Golgi glycosyltransferases are probably degraded by the ecto-domain shedding. We discovered that most glycosyltransferases are not retrieved from post-Golgi sites, indicating that retention but not retrieval should be the main mechanism for their Golgi localization. We proposed to use the Golgi residence time to study the Golgi retention of glycosyltransferases quantitatively and systematically. Various chimeras between ST6GAL1 and either transferrin receptor or tumor necrosis factor α quantitatively revealed the contributions of three regions of ST6GAL1, namely the N-terminal cytosolic tail, transmembrane domain and ecto-domain, to the Golgi retention. We found that each of the three regions is sufficient to produce a retention in an additive manner. The N-terminal cytosolic tail length negatively affects the Golgi retention of ST6GAL1, similar to what is known of the transmembrane domain. Therefore, long N-terminal cytosolic tail and transmembrane domain can be a Golgi export signal for transmembrane secretory cargos.

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Shedding of the Transferrin Receptor Is Mediated Constitutively by an Integral Membrane Metalloprotease Sensitive to Tumor Necrosis Factor α Protease Inhibitor-2

Journal of Biological Chemistry ◽

10.1074/jbc.m203461200 ◽

2002 ◽

Vol 277 (41) ◽

pp. 38494-38502 ◽

Cited By ~ 30

Author(s):

Matthias Kaup ◽

Katrin Dassler ◽

Christoph Weise ◽

Hendrik Fuchs

Keyword(s):

Tumor Necrosis Factor ◽

Protease Inhibitor ◽

Transferrin Receptor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Factor Α ◽

Necrosis Factor ◽

Membrane Metalloprotease

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Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding

Journal of Cell Science ◽

10.1242/jcs.112.21.3603 ◽

1999 ◽

Vol 112 (21) ◽

pp. 3603-3617 ◽

Cited By ~ 13

Author(s):

J. Schlondorff ◽

C.P. Blobel

Keyword(s):

Tumor Necrosis ◽

Ectodomain Shedding ◽

Membrane Glycoproteins ◽

Tnf Α ◽

Disintegrin Domain ◽

Protein Ectodomain Shedding ◽

Integrin Ligands ◽

Factor Α ◽

Necrosis Factor

Metalloprotease-disintegrins (ADAMs) have captured our attention as key players in fertilization and in the processing of the ectodomains of proteins such as tumor necrosis factor (α) (TNF(α)), and because of their roles in Notch-mediated signaling, neurogenesis and muscle fusion. ADAMs are integral membrane glycoproteins that contain a disintegrin domain, which is related to snake-venom integrin ligands, and a metalloprotease domain (which can contain or lack a catalytic site). Here, we review and critically discuss current topics in the ADAMs field, including the central role of fertilin in fertilization, the role of the TNF(α) convertase in protein ectodomain processing, the role of Kuzbanian in Notch signaling, and links between ADAMs and processing of the amyloid-precursor protein.

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