Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics

Autor: Kamal M. Khanna, Leo Lefrançois, Timothy Hla, Caiying Guo, Victoria A. Blaho, Shobha Thangada, Myat Lin Oo, Dong Soon Im
Rok vydání: 2010
Předmět:
Agonist
Adoptive cell transfer
medicine.drug_class
Sphingosine-1-phosphate receptor
media_common.quotation_subject
Lymphocyte
T-Lymphocytes
Immunology
Molecular Sequence Data
Biology
Article
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Sphingosine
Lymphopenia
medicine
Immunology and Allergy
Animals
Internalization
Receptor
030304 developmental biology
media_common
0303 health sciences
Base Sequence
Fingolimod Hydrochloride
organic chemicals
Cell Membrane
Endocytosis
Cell biology
Mice
Inbred C57BL
Chemotaxis
Leukocyte
Kinetics
Receptors
Lysosphingolipid
medicine.anatomical_structure
chemistry
Amino Acid Substitution
Propylene Glycols
lipids (amino acids
peptides
and proteins)
Mutant Proteins
Signal transduction
Lysophospholipids
030217 neurology & neurosurgery
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
Popis: The sphingosine 1-phosphate receptor 1 (S1P(1)) promotes lymphocyte egress from lymphoid organs. Previous work showed that agonist-induced internalization of this G protein-coupled receptor correlates with inhibition of lymphocyte egress and results in lymphopenia. However, it is unclear if S1P(1) internalization is necessary for this effect. We characterize a knockin mouse (S1p1r(S5A/S5A)) in which the C-terminal serine-rich S1P(1) motif, which is important for S1P(1) internalization but dispensable for S1P(1) signaling, is mutated. T cells expressing the mutant S1P(1) showed delayed S1P(1) internalization and defective desensitization after agonist stimulation. Mutant mice exhibited significantly delayed lymphopenia after S1P(1) agonist administration or disruption of the vascular S1P gradient. Adoptive transfer experiments demonstrated that mutant S1P(1) expression in lymphocytes, rather than endothelial cells, facilitated this delay in lymphopenia. Thus, cell-surface residency of S1P(1) on T cells is a primary determinant of lymphocyte egress kinetics in vivo.
Databáze: OpenAIRE
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