Spinophilin participates in information transfer at immunological synapses

Ona Bloom^1,2, Julia J. Unternaehrer^1,2, Aimin Jiang^1,2, Jeong-Sook Shin^1,2, Lélia Delamarre⁴, Patrick Allen³, , and Ira Mellman⁴

¹ Department of Cell Biology and ² Department of Immunobiology, Ludwig Institute for Cancer Research, and ³ Department of Psychiatry, Yale School of Medicine, New Haven, CT 06520
⁴ Genentech, Inc., South San Francisco, CA 94080

Correspondence to I. Mellman: mellman.ira{at}gene.com

Abstract: The adaptive immune response is initiated by the presentation of peptides bound to major histocompatibility complex molecules on dendritic cells (DCs) to antigen-specific T lymphocytes at a junction termed the immunological synapse. Although much attention has been paid to cytoplasmic events on the T cell side of the synapse, little is known concerning events on the DC side. We have sought signal transduction components of the neuronal synapse that were also expressed by DCs. One such protein is spinophilin, a scaffolding protein of neuronal dendritic spines that regulates synaptic transmission. In inactive, immature DCs, spinophilin is located throughout the cytoplasm but redistributes to the plasma membrane upon stimulus-induced maturation. In DCs interacting with T cells, spinophilin is polarized dynamically to contact sites in an antigen-dependent manner. It is also required for optimal T cell activation because DCs derived from mice lacking spinophilin exhibit defects in antigen presentation both in vitro and in vivo. Thus, spinophilin may play analogous roles in information transfer at both neuronal and immunological synapses.

O. Bloom's present address is The Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, NY 11030.

J.J. Unternaehrer's present address is Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02115.

A. Jiang's present address is Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520.

J.-S. Shin's present address is Department of Immunobiology, University of California, San Francisco, San Francisco, CA 94143.

Abbreviations used in this paper: APC, antigen-presenting cell; BMDC, bone marrow–derived dendritic cell; CFSE, 5(6)-carboxyfluorescein diacetate N-succinimidyl ester; DC, dendritic cell; GPCR, G protein–coupled receptor; IL-2, interleukin-2; IS, immunological synapse; KO, knockout; LPS, lipopolysaccharide; MHCII, major histocompatibility complex type II; PP1, protein phosphatase I; ROI, region of interest; TCR, T cell receptor; WT, wild type.

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