Arf6 and Rab22 mediate T cell conjugate formation by regulating clathrin-independent endosomal membrane trafficking

Johnson, Debra; Wayt, Jessica; Wilson, Jean M.; Donaldson, Julie G.

doi:10.1242/jcs.200477

Cited by 26 publications

(28 citation statements)

References 49 publications

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“…As in most of the pertinent literature, the experimental system was HeLa cells, and the antibody used to detect class I was W6/32, which detects HLA heavy chains bound to β 2 m. In this system, class I localized to tubulo-vesicular structures decorated with Arf6. Moreover, in HeLa and Jurkat cells where the constitutively active mutant Arf6 Q67L was overexpressed, internalized class I molecules accumulated in PIP 2 rich endosomes, thereby preventing their further degradation or recycling (13, 39, 40). Furthermore, overexpression of an effector domain mutant of Arf6 (N48I) in HeLa cells decreased recycling of class I molecules by 60% relative to control cells (35).…”

Section: Recycling Of Fully Conformed Mhc Class I Molecules: Methods mentioning

confidence: 99%

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Montealegre

Endert

2019

Front. Immunol.

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Major histocompatibility complex class I (MHC I) molecules are glycoproteins that display peptide epitopes at the cell surface of nucleated cells for recognition by CD8+ T cells. Like other cell surface receptors, MHC class I molecules are continuously removed from the surface followed by intracellular degradation or recycling to the cell surface, in a process likely involving active quality control the mechanism of which remains unknown. The molecular players and pathways involved in internalization and recycling have previously been studied in model cell lines such as HeLa. However, dendritic cells (DCs), which rely on a specialized endocytic machinery that confers them the unique ability to “cross”-present antigens acquired by internalization, may use distinct MHC I recycling pathways and quality control mechanisms. By providing MHC I molecules cross-presenting antigens, these pathways may play an important role in one of the key functions of DCs, priming of T cell responses against pathogens and tumors. In this review, we will focus on endocytic recycling of MHC I molecules in various experimental conditions and cell types. We discuss the organization of the recycling pathway in model cell lines compared to DCs, highlighting the differences in the recycling rates and pathways of MHC I molecules between various cell types, and their putative functional consequences. Reviewing the literature, we find that conclusive evidence for significant recycling of MHC I molecules in primary DCs has yet to be demonstrated. We conclude that endocytic trafficking of MHC class I in DCs remains poorly understood and should be further studied because of its likely role in antigen cross-presentation.

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Section: Recycling Of Fully Conformed Mhc Class I Molecules: Methods mentioning

confidence: 99%

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Montealegre

Endert

2019

Front. Immunol.

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“…Upon internalization, a series of steps determine the fate of intracellular LFA-1 (degradation vs. recycling). Integrins are generally thought to return to the cell surface through via either a direct exocytosis route ( via Rab4 or Rab5) or the perinuclear recycling compartment route ( via Rab11) ( 69 , 71 , 72 ). LFA-1 containing vesicles during T-antigen-presenting cell (APC) interactions have also been found to require Arf6 + Rab22 ( 72 ).…”

Section: Lfa-1 and T Cell Migrationmentioning

confidence: 99%

“…Integrins are generally thought to return to the cell surface through via either a direct exocytosis route ( via Rab4 or Rab5) or the perinuclear recycling compartment route ( via Rab11) ( 69 , 71 , 72 ). LFA-1 containing vesicles during T-antigen-presenting cell (APC) interactions have also been found to require Arf6 + Rab22 ( 72 ). LFA-1 can specifically utilize a Rab13-dependent pathway through which Rab13 associates with Mst1 to facilitate increased integrin activation, as evidenced by increased LFA-1 clustering and cell migration ( 69 , 73 ).…”

Section: Lfa-1 and T Cell Migrationmentioning

confidence: 99%

LFA-1 in T Cell Migration and Differentiation

2018

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Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration. With 24 integrin pairs having been discovered to date, integrins are defined not only by the composition of the heterodimeric pair but by cell-type specific expression and their ligands. Furthermore, integrins not only facilitate adhesion but also induce intracellular signaling and have recently been uncovered as mechanosensors providing additional complexity to the signaling pathways. Among several leukocyte-specific integrins, lymphocyte function-associated antigen-1 (LFA-1 or αLβ2; CD11a/CD18) is a key T cell integrin, which plays a major role in regulating T cell activation and migration. Adhesion to LFA-1’s ligand, intracellular adhesion receptor 1 (ICAM-1) facilitates firm endothelium adhesion, prolonged contact with antigen-presenting cells, and binding to target cells for killing. While the downstream signaling pathways utilized by LFA-1 are vastly conserved they allow for highly disparate responses. Here, we summarize the roles of LFA-1 and ongoing studies to better understand its functions and regulation.

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“…Studies have found that the RAB5 subfamily (including RAB5, RAB21, RAB22A and RAB22B) is mainly involved in the endocytosis, transport and metabolism of growth factor receptors, and may thus be associated with cancer progression (13)(14)(15). In different cell lines, RAB22A is known as an endosomal-associated protein, involved in exocrine vehicle formation (16,17). At the plasma membrane of MDA-MB-231 cells, RAB22A has been shown to be a component of microvesicles.…”

Section: Introductionmentioning

confidence: 99%

Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes

Sun

et al. 2018

Int J Oncol

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Breast cancer is one of the main types of cancer affecting the health of females worldwide. Despite improvements in therapeutic approaches, cancer patients succumb to the disease due to metastasis itself, rather than the primary tumor from which metastases arise, emphasizing the need for the better understanding of the biological bases that contribute to disease progression. RAB22A, a member of the proto-oncogene RAS family, plays an important role in the formation, trafficking and metabolism of exosomes, and is associated with the occurrence and development of multiple human cancers. In this study, we demonstrate that the upregulation of RAB22A is associated with breast cancer progression and lymph node metastasis. We identified a signature of RAB22A and miR-193b that exhibited a negative association in metastatic as opposed to the surrounding normal cells, and RAB22A was identified as the target gene of miR-193b. While RAB22A was found to regulate exosomes-mediated breast cancer cell proliferation, invasion and migration, these biological characteristics were diminished in the breast cancer cells in which the RAB22A gene was knocked down or in the cells in which the exosomes were dissolved by proteinase K/RNase treatment. On the whole, the findings of this study demonstrate the critical role that miR-193b plays in the regulation of RAB22A-mediated exosome function during cancer growth and metastasis, which may have significant implications on cancer therapy.

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Arf6 and Rab22 mediate T cell conjugate formation by regulating clathrin-independent endosomal membrane trafficking

Cited by 26 publications

References 49 publications

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

LFA-1 in T Cell Migration and Differentiation

Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes

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