Universität zu Köln

Tamzalit, Fella, Tran, Diana, Jin, Weiyang, Boyko, Vitaly, Bazzi, Hisham ORCID: 0000-0001-8388-4005, Kepecs, Ariella, Kam, Lance C., Anderson, Kathryn V. and Huse, Morgan (2020). Centrioles control the capacity, but not the specificity, of cytotoxic T cell killing. Proc. Natl. Acad. Sci. U. S. A., 117 (8). S. 4310 - 4320. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Immunological synapse formation between cytotoxic T lymphocytes (CTLs) and the target cells they aim to destroy is accompanied by reorientation of the CTL centrosome to a position beneath the synaptic membrane. Centrosome polarization is thought to enhance the potency and specificity of killing by driving lytic granule fusion at the synapse and thereby the release of perforin and granzymes toward the target cell. To test this model, we employed a genetic strategy to delete centrioles, the core structural components of the centrosome. Centriole deletion altered microtubule architecture as expected but surprisingly had no effect on lytic granule polarization and directional secretion. Nevertheless, CTLs lacking centrioles did display substantially reduced killing potential, which was associated with defects in both lytic granule biogenesis and synaptic actin remodeling. These results reveal an unexpected role for the intact centrosome in controlling the capacity but not the specificity of cytotoxic killing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tamzalit, Fella UNSPECIFIED UNSPECIFIED UNSPECIFIED Tran, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Jin, Weiyang UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyko, Vitaly UNSPECIFIED UNSPECIFIED UNSPECIFIED Bazzi, Hisham UNSPECIFIED orcid.org/0000-0001-8388-4005 UNSPECIFIED Kepecs, Ariella UNSPECIFIED UNSPECIFIED UNSPECIFIED Kam, Lance C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Anderson, Kathryn V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huse, Morgan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-344078
DOI:	10.1073/pnas.1913220117
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	117
Number:	8
Page Range:	S. 4310 - 4320
Date:	2020
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MICROTUBULE-ORGANIZING CENTER; IMMUNOLOGICAL SYNAPSE; CENTROSOME DOCKING; GRANULE SECRETION; POLARIZATION; PROTEIN; CONTRIBUTES; INSTABILITY; MECHANISMS; DEPLETION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34407