التفاصيل البيبلوغرافية
| العنوان: |
Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells |
| المؤلفون: |
Ifie, Eseoghene, Russell, Mark M.A., Dhayal, Shalinee, Leete, Pia, Sebastiani, Guido, Nigi, Laura, Dotta, Francesco, Marjomäki, Varpu, Eizirik, Decio L., Morgan, Noël N.G., Richardson, Sarah S.J. |
| المصدر: |
Diabetologia, 61 (11 |
| سنة النشر: |
2018 |
| المجموعة: |
DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: |
Médecine interne, Endocrinologie, Diabétologie, Métabolisme, Beta cells, Coxsackie and adenovirus receptor, Coxsackievirus B, Enterovirus, Insulin granule, Pancreas, Protein interacting with C-kinase 1 (PICK1) |
| الوصف: |
Aims/hypothesis: The Coxsackie and adenovirus receptor (CAR) is a transmembrane cell-adhesion protein that serves as an entry receptor for enteroviruses and may be essential for their ability to infect cells. Since enteroviral infection of beta cells has been implicated as a factor that could contribute to the development of type 1 diabetes, it is often assumed that CAR is displayed on the surface of human beta cells. However, CAR exists as multiple isoforms and it is not known whether all isoforms subserve similar physiological functions. In the present study, we have determined the profile of CAR isoforms present in human beta cells and monitored the subcellular localisation of the principal isoform within the cells. Methods: Formalin-fixed, paraffin-embedded pancreatic sections from non-diabetic individuals and those with type 1 diabetes were studied. Immunohistochemistry, confocal immunofluorescence, electron microscopy and western blotting with isoform-specific antisera were employed to examine the expression and cellular localisation of the five known CAR isoforms. Isoform-specific qRT-PCR and RNA sequencing (RNAseq) were performed on RNA extracted from isolated human islets. Results: An isoform of CAR with a terminal SIV motif and a unique PDZ-binding domain was expressed at high levels in human beta cells at the protein level. A second isoform, CAR-TVV, was also present. Both forms were readily detected by qRT-PCR and RNAseq analysis in isolated human islets. Immunocytochemical studies indicated that CAR-SIV was the principal isoform in islets and was localised mainly within the cytoplasm of beta cells, rather than at the plasma membrane. Within the cells it displayed a punctate pattern of immunolabelling, consistent with its retention within a specific membrane-bound compartment. Co-immunofluorescence analysis revealed significant co-localisation of CAR-SIV with zinc transporter protein 8 (ZnT8), prohormone convertase 1/3 (PC1/3) and insulin, but not proinsulin. This suggests that CAR-SIV may be ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
1 full-text file(s): application/pdf |
| اللغة: |
English |
| العلاقة: |
uri/info:doi/10.1007/s00125-018-4704-1; uri/info:pmid/30074059; uri/info:scp/85050582194; https://dipot.ulb.ac.be/dspace/bitstream/2013/280148/1/doi_263775.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/280148Test |
| الإتاحة: |
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/280148Test |
| رقم الانضمام: |
edsbas.8D64C7F1 |
| قاعدة البيانات: |
BASE |
