uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Different Munc13 isoforms function as priming factors in lytic granule release from murine cytotoxic T lymphocytes.
Show others and affiliations
2013 (English)In: Traffic: the International Journal of Intracellular Transport, ISSN 1398-9219, E-ISSN 1600-0854, Vol. 14, no 7Article in journal (Refereed) Published
Abstract [en]

In order to fuse lytic granules (LGs) with the plasma membrane at the immunological synapse, cytotoxic T lymphocytes (CTLs) have to render these LGs fusion-competent through the priming process. In secretory tissues such as brain and neuroendocrine glands, this process is mediated by members of the Munc13 protein family. In human CTLs, mutations in the Munc13-4 gene cause a severe loss in killing efficiency, resulting in familial hemophagocytic lymphohistiocytosis type 3, suggesting a similar role of other Munc13 isoforms in the immune system. Here, we investigate the contribution of different Munc13 isoforms to the priming process of murine CTLs at both the mRNA and protein level. We demonstrate that Munc13-1 and Munc13-4 are the only Munc13 isoforms present in mouse CTLs. Both isoforms rescue the drastical secretion defect of CTLs derived from Munc13-4-deficient Jinx mice. Mobility studies using total internal reflection fluorescence microscopy indicate that Munc13-4 and Munc13-1 are responsible for the priming process of LGs. Furthermore, the domains of the Munc13 protein, which is responsible for functional fusion, could be identified. We conclude from these data that both isoforms of the Munc13 family, Munc13-1 and Munc13-4, are functionally redundant in murine CTLs.

Place, publisher, year, edition, pages
2013. Vol. 14, no 7
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-298307DOI: 10.1111/tra.12074ISI: 000320180400006PubMedID: 23590328OAI: oai:DiVA.org:uu-298307DiVA: diva2:945615
Available from: 2016-07-01 Created: 2016-07-01 Last updated: 2016-08-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Marshall, Misty R
In the same journal
Traffic: the International Journal of Intracellular Transport
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 23 hits
ReferencesLink to record
Permanent link

Direct link