PirB restricts ocular-dominance plasticity in visual cortex.
Experience can alter synaptic connectivity throughout life, but the degree of plasticity present at each age is regulated by mechanisms that remain largely unknown. Here, we demonstrate that Paired-immunoglobulin-like receptor B (PirB), a major histocompatibility complex class I (MHCI) receptor, is expressed in subsets of neurons throughout the brain. Neuronal PirB protein is associated with synapses and forms complexes with the phosphatases Shp-1 and Shp-2. Soluble PirB fusion protein binds to cortical neurons in an MHCI-dependent manner. In mutant mice lacking functional PirB, cortical ocular-dominance plasticity is more robust at all ages. Thus, an MHCI receptor is expressed in central nervous system neurons and functions to limit the extent of experience-dependent plasticity in the visual cortex throughout life. PirB is also expressed in many other regions of the central nervous system, suggesting that it may function broadly to stabilize neural circuits.
Syken
Josh
J
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Grandpre
Tadzia
T
Kanold
Patrick O
PO
Shatz
Carla J
CJ
D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D023882:Dominance, Ocular / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D014793:Visual Cortex / Q000502:physiology*
D003598:Cytoskeletal Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C092069:activity regulated cytoskeletal-associated protein; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse