Dataset Information

SNX27 interactome during immune synapse formation

ABSTRACT: T lymphocyte recognition of antigenic peptides on the surface of antigen-presenting cells (APC) leads to immune synapse formation (IS). By analogy with the nervous synapse, this cell-cell communication model requires the formation of highly organized structures that delimit an active zone of membrane traffic. For T cells to connect antigen recognition with the biological response, receptors and signaling proteins must be recycled. Sorting nexin 27 (SNX27) is an endosomal protein best known for its role in recycling PDZ (PSD95, Dlg1, ZO-1)-interacting neuronal proteins via the retromer transport machinery. Alteration of this sorting pathway leads to neurodegeneration and is associated to Down syndrome, Alzheimer’s and Parkinson’s diseases. In T lymphocytes, SNX27 interacts with diacylglycerol kinase zeta (DGKz), which provides a mechanistic link between diacylglycerol metabolism and membrane trafficking. Following antigen recognition, SNX27-positive endosomes polarize to the IS and a PDZ-dependent SNX27 pool accumulates at the cell-cell contact area. To test for additional SNX27 functions, we carried out proteomic analysis of the SNX27 interactome purified from T cells in contact with APC, and identified SNX27 interaction with the retromer and with members of the WASH (Wiskott-Aldrich syndrome protein and SCAR homologue) complex. This finding indicates the conserved nature of the SNX27/WASH/retromer complex in hematopoietic cells and suggests similarity between neurological diseases and abnormal immune/inflammatory responses. We also found PDZ-dependent SNX27 cargoes, including modulators of cytoskeletal reorganization such as zona occludens-2 (ZO-2). ZO-2, a cytosolic component of epithelial cell-cell junctions, localized to the IS, and SNX27 silencing affected ZO-2 stability at the synapse. This study broadens our knowledge of SNX27 function in T lymphocytes, and suggests that pathways that delimit polarized structures in epithelial systems also participate in IS regulation.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Jurkat Cell

SUBMITTER: Gonzalo Martínez

LAB HEAD: Isabel Mérida

PROVIDER: PXD003628 | Pride | 2017-05-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	030615_SNXIP_Mut_band1.dat-pride.pride.mgf.gz	Mgf
	030615_SNXIP_Mut_band1.dat-pride.pride.mztab.gz	Mztab
	030615_SNXIP_Mut_band1.dat-pride.xml.gz	Xml
	030615_SNXIP_Mut_band1.mgf	Mgf
	030615_SNXIP_Mut_band1.wiff	Wiff

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Publications

Sorting nexin 27 interactome in T-lymphocytes identifies zona occludens-2 dynamic redistribution at the immune synapse.

Tello-Lafoz María M Martínez-Martínez Gonzalo G Rodríguez-Rodríguez Cristina C Albar Juan Pablo JP Huse Morgan M Gharbi Severine S Merida Isabel I

Traffic (Copenhagen, Denmark) 20170629 8

T Lymphocyte recognition of antigens leads to the formation of a highly organized structure termed immune synapse (IS) by analogy with the neuronals synapse. Sorting nexin 27 (SNX27) controls the endosomal traffic of PSD95, Dlg1, ZO-1 (PDZ) domain-interacting proteins, and its alteration is associated with impaired synaptic function and neurological diseases. In T-lymphocytes, SNX27-positive vesicles polarize to the IS, the identity of SNX27 interactors in these conditions nonetheless remains un ...[more]

PMID: 28477369

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