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ScFv antibody-induc...
ScFv antibody-induced translocation of cell-surface heparan sulfate proteoglycan to endocytic vesicles: Evidence for heparan sulfate epitope specificity and role of both syndecan and glypican.
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- Wittrup, Anders (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Zhang, Sihe (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Ten Dam, Gerdy B (författare)
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van Kuppevelt, Toin H (författare)
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- Bengtson, Per (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Johansson, Maria C (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Welch, Johanna (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Mörgelin, Matthias (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Belting, Mattias (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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(creator_code:org_t)
- 2009
- 2009
- Engelska.
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 284:47, s. 32959-32967
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cellular uptake of several viruses and polybasic macromolecules requires the expression of cell-surface heparan sulfate proteoglycan (HSPG) through as yet ill-defined mechanisms. We unexpectedly found that among several cell-surface binding scFv anti-HS antibody (alphaHS) clones only one, AO4B08, efficiently translocated macromolecular cargo to intracellular vesicles through induction of HSPG endocytosis. Interestingly, AO4B08-induced PG internalization was strictly dependent on HS 2-O-sulfation and appeared independent on intact N-sulfation. AO4B08 and HIV-tat, i.e. a well-known cell penetrating peptide, were shown to compete for the internalizing PG population. To obtain a more detailed characterization of this pathway, we have developed a procedure for the isolation of endocytic vesicles by conjugating AO4B08 with superparamagnetic nano-particles. [35S]sulfate-labelled HSPG was found to accumulate in isolated, AO4B08-containing vesicles, providing first biochemical evidence for intact HSPG co-internalization with its ligand. Further analysis revealed the existence of both syndecan, i.e. a transmembrane HSPG, and glycosylphosphatidyl- inositol anchored glypican in purified vesicles. Importantly, internalized syndecan and glypican were found to colocalize in AO4B08-containing vesicles. Our data establish HSPGs as true internalizing receptors of macromolecular cargo, and indicate that the sorting of cell-surface HSPG to endocytic vesicles is determined by a specific HS epitope that can be carried by both syndecan and glypican core protein.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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