MHCI Negatively Regulates Synapse Density During the Establishment of Cortical Connections

Overview

Journal Nat Neurosci

Date 2011 Mar 2

PMID 21358642

Citations 106

Authors

Marian W Glynn

Bradford M Elmer

Paula A Garay

Xiao-Bo Liu

Leigh A Needleman

Faten El-Sabeawy

A Kimberley McAllister

Affiliations

Soon will be listed here.

Abstract

Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. We found that MHCI also negatively regulates the density and function of cortical synapses during their initial establishment both in vitro and in vivo. MHCI molecules are expressed on cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increased glutamatergic and GABAergic synapse density, whereas overexpression decreased it. In vivo, synapse density was higher throughout development in β2m(-/-) mice. MHCI also negatively regulated the strength of excitatory, but not inhibitory, synapses and controlled the balance of excitation and inhibition onto cortical neurons. sMHCI levels were modulated by activity and were necessary for activity to negatively regulate glutamatergic synapse density. Finally, acute changes in sMHCI and activity altered synapse density exclusively during early postnatal development. These results identify a previously unknown function for immune proteins in the negative regulation of the initial establishment and function of cortical connections.

Citing Articles

Dendritic growth and synaptic organization from activity-independent cues and local activity-dependent plasticity.

Kirchner J, Euler L, Fritz I, Ferreira Castro A, Gjorgjieva J Elife. 2025; 12.

PMID: 39899359 PMC: 11790248. DOI: 10.7554/eLife.87527.

Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.

Tsourmas K, Butler C, Kwang N, Sloane Z, Dykman K, Maloof G bioRxiv. 2024; .

PMID: 39484433 PMC: 11526954. DOI: 10.1101/2024.10.21.619538.

Glutamate Signaling and Neuroligin/Neurexin Adhesion Play Opposing Roles That Are Mediated by Major Histocompatibility Complex I Molecules in Cortical Synapse Formation.

Sell G, Barrow S, Kimberley McAllister A J Neurosci. 2024; 44(49).

PMID: 39424368 PMC: 11622183. DOI: 10.1523/JNEUROSCI.0797-24.2024.

HLA-A, -B, -C and -DRB1 Association with Autism Spectrum Disorder Risk: A Sex-Related Analysis in Italian ASD Children and Their Siblings.

Guerini F, Bolognesi E, Mensi M, Zanette M, Agliardi C, Zanzottera M Int J Mol Sci. 2024; 25(18).

PMID: 39337366 PMC: 11431861. DOI: 10.3390/ijms25189879.

CD8 T cells exacerbate AD-like symptoms in mouse model of amyloidosis.

Wang X, Campbell B, Bodogai M, McDevitt R, Patrikeev A, Gusev F Brain Behav Immun. 2024; 122:444-455.

PMID: 39191349 PMC: 11409913. DOI: 10.1016/j.bbi.2024.08.045.

References

Kimberley McAllister A . Dynamic aspects of CNS synapse formation. Annu Rev Neurosci. 2007; 30:425-50. PMC: 3251656. DOI: 10.1146/annurev.neuro.29.051605.112830. View

Flavell S, Cowan C, Kim T, Greer P, Lin Y, Paradis S . Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science. 2006; 311(5763):1008-12. DOI: 10.1126/science.1122511. View

Patterson P . Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Curr Opin Neurobiol. 2002; 12(1):115-8. DOI: 10.1016/s0959-4388(02)00299-4. View

Craig A, Blackstone C, Huganir R, Banker G . Selective clustering of glutamate and gamma-aminobutyric acid receptors opposite terminals releasing the corresponding neurotransmitters. Proc Natl Acad Sci U S A. 1994; 91(26):12373-7. PMC: 45440. DOI: 10.1073/pnas.91.26.12373. View

Williams D, Barber B, Flavell R, Allen H . Role of beta 2-microglobulin in the intracellular transport and surface expression of murine class I histocompatibility molecules. J Immunol. 1989; 142(8):2796-806. View

Naranda T, Goldstein A, Olsson L . A peptide derived from an extracellular domain selectively inhibits receptor internalization: target sequences on insulin and insulin-like growth factor 1 receptors. Proc Natl Acad Sci U S A. 1997; 94(21):11692-7. PMC: 23593. DOI: 10.1073/pnas.94.21.11692. View

Shi L, Fatemi S, Sidwell R, Patterson P . Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci. 2003; 23(1):297-302. PMC: 6742135. View

Rao A, Craig A . Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons. Neuron. 1997; 19(4):801-12. DOI: 10.1016/s0896-6273(00)80962-9. View

Lauri S, Lamsa K, Pavlov I, Riekki R, Johnson B, Molnar E . Activity blockade increases the number of functional synapses in the hippocampus of newborn rats. Mol Cell Neurosci. 2003; 22(1):107-17. DOI: 10.1016/s1044-7431(02)00012-x. View

10.

Needleman L, Liu X, El-Sabeawy F, Jones E, Kimberley McAllister A . MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood. Proc Natl Acad Sci U S A. 2010; 107(39):16999-7004. PMC: 2947898. DOI: 10.1073/pnas.1006087107. View

11.

Fishman D, Elhyany S, Segal S . Non-immune functions of MHC class I glycoproteins in normal and malignant cells. Folia Biol (Praha). 2004; 50(2):35-42. View

12.

Hartman K, Pal S, Burrone J, Murthy V . Activity-dependent regulation of inhibitory synaptic transmission in hippocampal neurons. Nat Neurosci. 2006; 9(5):642-9. DOI: 10.1038/nn1677. View

13.

Cochilla A, Angleson J, Betz W . Monitoring secretory membrane with FM1-43 fluorescence. Annu Rev Neurosci. 1999; 22:1-10. DOI: 10.1146/annurev.neuro.22.1.1. View

14.

Olsson L, Goldstein A, Stagsted J . Regulation of receptor internalization by the major histocompatibility complex class I molecule. Proc Natl Acad Sci U S A. 1994; 91(19):9086-90. PMC: 44752. DOI: 10.1073/pnas.91.19.9086. View

15.

Wierenga C, Walsh M, Turrigiano G . Temporal regulation of the expression locus of homeostatic plasticity. J Neurophysiol. 2006; 96(4):2127-33. DOI: 10.1152/jn.00107.2006. View

16.

Patel M, Shen K . RSY-1 is a local inhibitor of presynaptic assembly in C. elegans. Science. 2009; 323(5920):1500-3. PMC: 3087376. DOI: 10.1126/science.1169025. View

17.

DeFelipe J, Marco P, Busturia I, Merchan-Perez A . Estimation of the number of synapses in the cerebral cortex: methodological considerations. Cereb Cortex. 1999; 9(7):722-32. DOI: 10.1093/cercor/9.7.722. View

18.

Boulanger L, Shatz C . Immune signalling in neural development, synaptic plasticity and disease. Nat Rev Neurosci. 2004; 5(7):521-31. DOI: 10.1038/nrn1428. View

19.

Neumann H, Schmidt H, Cavalie A, Jenne D, Wekerle H . Major histocompatibility complex (MHC) class I gene expression in single neurons of the central nervous system: differential regulation by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. J Exp Med. 1997; 185(2):305-16. PMC: 2196130. DOI: 10.1084/jem.185.2.305. View

20.

Glynn M, Kimberley McAllister A . Immunocytochemistry and quantification of protein colocalization in cultured neurons. Nat Protoc. 2007; 1(3):1287-96. DOI: 10.1038/nprot.2006.220. View