Proteoglycan biosynthesis in chondrocytes: protein A-gold localization of proteoglycan protein core and chondroitin sulfate within Golgi subcompartments.

Ratcliffe, Anthony; Fryer, P.; Hardingham, Timothy E.

doi:10.1083/jcb.101.6.2355

Cited by 45 publications

(23 citation statements)

References 69 publications

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“…The PG-forming site in Xenopus epidermal cells is presumably the Golgi apparatus, the same as cartilage PG (Sugumaran and Silbert, 1991;Burditt et al, 1985;Ratcliffe et al, 1984Ratcliffe et al, ,1985. In this study, however, only a few gold particles derived from the presence of C6S and COS were observed in the Golgi cisternae.…”

Section: Discussioncontrasting

confidence: 47%

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Secretion of chondroitin sulfate from embryonic epidermal cells in Xenopus laevis.

Nishikawa¹,

Sasaki²

1993

J Histochem Cytochem.

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Section: Discussioncontrasting

confidence: 47%

“…The site of core protein synthesis of PG is considered to be rough endoplasmic reticulum, and the protein is transported to the Golgi apparatus. Glycosylation and sulfation occur in the Golgi apparatus and/or the trans-Golgi network (Sugumaran et al, 1992;Blair et al, 1991;Spiro et al, 1991;Ratcliffe et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Secretion of chondroitin sulfate from embryonic epidermal cells in Xenopus laevis.

Nishikawa¹,

Sasaki²

1993

J Histochem Cytochem.

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“…These data are in agreement with the widespread idea that sulfate addition is a late Golgi modification. Consistent with this view is the fact that sulfated GAGs have been identified by cytochemical (20,21) and immunoelectron microscopy techniques (22) in the medial-and trans-, but not the cis-, cisternae of the Golgi complex.…”

supporting

confidence: 62%

In Vitro Synthesis of Sulfated Glycosaminoglycans Coupled to Inter-compartmental Golgi Transport

Fernández

Warren

1998

Journal of Biological Chemistry

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We have used isolated rat liver Golgi membranes to reconstitute the synthesis of sulfated glycosaminoglycans (GAGs) onto the membrane-permeable, external acceptor xyloside. Biosynthetic labeling of GAGs with [ 35 S]sulfate in vitro is shown to have an absolute requirement for ATP and cytosolic proteins and is inhibited by dismantling the Golgi apparatus with okadaic acid or under mitotic conditions suggesting that intercompartmental transport between Golgi cisternae is a prerequisite for the successful completion of the initiation, polymerization, and sulfation of GAGs. Accordingly, we show that in vitro synthesis of 35 S-GAGs utilizes the same machinery employed in Golgi transport events in terms of vesicle budding (ADP-ribosylation factor and coatomer), docking (Rabs), targeting (SNAREs), and fusion (N-ethylmaleimide-sensitive factor). This provides compelling evidence that GAGs synthesis is linked to Golgi membrane traffic and suggests that it can be used as a complementation-independent method to study membrane transport in Golgi preparations from any source. We have applied this system to show that intra-Golgi traffic requires the function of the Golgi target-SNARE, syntaxin 5.

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“…This is followed by more rapid translocation through the Golgi and by secretion within 5-10 min (26). Much evidence shows the addition of chondroitin sulfate and O-linked oligosaccharides to occur in the medial-trans-Golgi (27). The absence of any attached chondroitin sulfate in the cell layer product (Fig.…”

Section: Discussionmentioning

confidence: 99%

The Folded Protein Modules of the C-terminal G3 Domain of Aggrecan Can Each Facilitate the Translocation and Secretion of the Extended Chondroitin Sulfate Attachment Sequence

Day

Murdoch

Hardingham³

1999

Journal of Biological Chemistry

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Aggrecan is a multidomain proteoglycan containing both extended and folded protein modules. The C-terminal G3 domain contains a lectin-like, complement regulatory protein-like, and two alternatively spliced epidermal growth factor-like modules. It has been proposed that the lectin module alone has a necessary role in the intracellular translocation and secretion of proteins expressed containing G3. Constructs containing human aggrecan G3 together with 1155 bases of the adjacent chondroitin sulfate attachment region (CS-2) were prepared with different combinations and deletions of the protein modules and transfected into mammalian cells of monkey or hamster origin. The results showed that the products containing only the unfolded protein sequences (CS-2 with or without the C-terminal tail sequence) were translated and accumulated intracellularly but were not secreted. In contrast the constructs containing any of the folded protein modules and the extended CS-2 region were translated and secreted from the cells. The results show that the lectin module was not unique in facilitating the intracellular translocation and secretion of the G3 domain. The conservation of G3-like domains within the aggrecan family of proteoglycans may therefore result from their participation in other extracellular functions.Aggrecan is a large multidomain proteoglycan produced by chondrocytes and found as an essential component of the extracellular matrix of cartilage (1). The protein core consists of three globular and two extended domains. There is an Nterminal G1 domain that interacts specifically with hyaluronan to form multimolecular aggregates in which up to 100 aggrecan molecules bind to each hyaluronan chain (2). In contrast, the C-terminal G3 domain has no clearly established function. It consists of a C-type lectin module, a complement regulatory protein-like module and two alternatively spliced EGF 1 -like modules. Its structure is highly conserved among aggrecans in different species, and closely related structures are present in other members of this family of proteoglycans, versican, neurocan, and brevican (3). Its possible functions include both carbohydrate (4 -6) and protein ligand (7) interactions in the extracellular matrix, but it has also been proposed to have intracellular functions (8,9).The cause of nanomelia in the chicken was identified as a mutation in the aggrecan gene that produced a premature stop codon in the extended CS-2 chondroitin sulfate attachment region (10). This resulted in the synthesis of aggrecan lacking the normal C-terminal G3 structure, and although the protein was translated and present intracellularly in chondrocytes, it was not fully glycosylated or secreted (11,12). Cartilage is an essential forerunner of skeletal development in the embryo, and in the nanomelic chick the lack of aggrecan stunted cartilage development and long bone formation.These observations led to the proposal that the G3 domain was necessary intracellularly for the translocation and secretion of aggrecan. Expression of...

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Proteoglycan biosynthesis in chondrocytes: protein A-gold localization of proteoglycan protein core and chondroitin sulfate within Golgi subcompartments.

Cited by 45 publications

References 69 publications

Secretion of chondroitin sulfate from embryonic epidermal cells in Xenopus laevis.

Secretion of chondroitin sulfate from embryonic epidermal cells in Xenopus laevis.

In Vitro Synthesis of Sulfated Glycosaminoglycans Coupled to Inter-compartmental Golgi Transport

The Folded Protein Modules of the C-terminal G3 Domain of Aggrecan Can Each Facilitate the Translocation and Secretion of the Extended Chondroitin Sulfate Attachment Sequence

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