Variants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors.

Humans Intellectual Disability / genetics Autistic Disorder / genetics Aggression / physiology Male Female Child HEK293 Cells Neurons / metabolism Adolescent Membrane Proteins / genetics Adult Animals Child, Preschool Nerve Tissue Proteins / genetics Young Adult Synapses / metabolism PDZ Domains / genetics

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
10 Sep 2024

Historique:

received: 25 07 2023

accepted: 27 08 2024

medline: 11 9 2024

pubmed: 11 9 2024

entrez: 10 9 2024

Statut: epublish

Résumé

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca

Identifiants

DOI: 10.1038/s41467-024-52095-x PMID: 39256359

pubmed: 39256359

doi: 10.1038/s41467-024-52095-x

pii: 10.1038/s41467-024-52095-x

doi:

Substances chimiques

Membrane Proteins 0

Nerve Tissue Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

7909

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)

ID : Kr1321/9-1

Informations de copyright

Références

Santoni, M. J., Kashyap, R., Camoin, L. & Borg, J. P. The Scribble family in cancer: twentieth anniversary. Oncogene 39, 7019–7033 (2020).

pubmed: 32999444 pmcid: 7527152 doi: 10.1038/s41388-020-01478-7

Legouis, R. et al. LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans. Nat. Cell Biol. 2, 415–422 (2000).

pubmed: 10878806 doi: 10.1038/35017046

Bilder, D. & Perrimon, N. Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature 403, 676–680 (2000).

pubmed: 10688207 doi: 10.1038/35001108

Choi, J., Troyanovsky, R. B., Indra, I., Mitchell, B. J. & Troyanovsky, S. M. Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex. J. Cell Biol. 218, 2277–2293 (2019).

pubmed: 31147384 pmcid: 6605793 doi: 10.1083/jcb.201804201

Apperson, M. L., Moon, I. S. & Kennedy, M. B. Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. J. Neurosci. 16, 6839–6852 (1996).

pubmed: 8824323 pmcid: 6579252 doi: 10.1523/JNEUROSCI.16-21-06839.1996

Dosemeci, A., Tao-Cheng, J. H., Loo, H. & Reese, T. S. Distribution of densin in neurons. PLoS ONE 13, e0205859 (2018).

pubmed: 30325965 pmcid: 6191147 doi: 10.1371/journal.pone.0205859

Izawa, I., Nishizawa, M., Ohtakara, K. & Inagaki, M. Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses. J. Biol. Chem. 277, 5345–5350 (2002).

pubmed: 11729199 doi: 10.1074/jbc.M110052200

Quitsch, A., Berhorster, K., Liew, C. W., Richter, D. & Kreienkamp, H. J. Postsynaptic shank antagonizes dendrite branching induced by the leucine-rich repeat protein Densin-180. J. Neurosci. 25, 479–487 (2005).

pubmed: 15647492 pmcid: 6725485 doi: 10.1523/JNEUROSCI.2699-04.2005

Heikkila, E. et al. Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions. Mol. Cell Biochem. 305, 9–18 (2007).

pubmed: 17581699 doi: 10.1007/s11010-007-9522-6

Walikonis, R. S. et al. Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin. J Neurosci. 21, 423–433 (2001).

pubmed: 11160423 pmcid: 6763799 doi: 10.1523/JNEUROSCI.21-02-00423.2001

Jiao, Y. et al. Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation. J. Biol. Chem. 286, 24806–24818 (2011).

pubmed: 21610080 pmcid: 3137056 doi: 10.1074/jbc.M110.216010

Strack, S., Robison, A. J., Bass, M. A. & Colbran, R. J. Association of calcium/calmodulin-dependent kinase II with developmentally regulated splice variants of the postsynaptic density protein densin-180. J. Biol. Chem. 275, 25061–25064 (2000).

pubmed: 10827168 doi: 10.1074/jbc.C000319200

Carlisle, H. J. et al. Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction. J. Neurosci. 31, 16194–16207 (2011).

pubmed: 22072671 pmcid: 3235477 doi: 10.1523/JNEUROSCI.5877-10.2011

Chong, C. H. et al. Lrrc7 mutant mice model developmental emotional dysregulation that can be alleviated by mGluR5 allosteric modulation. Transl. Psychiatry. 9, 244 (2019).

pubmed: 31582721 pmcid: 6776540 doi: 10.1038/s41398-019-0580-9

Durand, C. M. et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39, 25–27 (2007).

pubmed: 17173049 doi: 10.1038/ng1933

Turner, T. N. et al. Loss of delta-catenin function in severe autism. Nature. 520, 51–56 (2015).

pubmed: 25807484 pmcid: 4383723 doi: 10.1038/nature14186

O’Roak, B. J. et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science. 338, 1619–1622 (2012).

pubmed: 23160955 pmcid: 3528801 doi: 10.1126/science.1227764

Hassani Nia, F. et al. Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans. Mol. Psych. 29, 1683–1697 (2024).

Greene, D. et al. Genetic association analysis of 77,539 genomes reveals rare disease etiologies. Nat. Med. 29, 679–688 (2023).

pubmed: 36928819 pmcid: 10033407 doi: 10.1038/s41591-023-02211-z

Popp, B. et al. Exome Pool-Seq in neurodevelopmental disorders. Eur. J. Hum. Genet. 25, 1364–1376 (2017).

pubmed: 29158550 pmcid: 5865117 doi: 10.1038/s41431-017-0022-1

Fu, J. M. et al. Broad institute center for common disease G, i P-BC, Cutler DJ, De Rubeis S, Buxbaum JD, Daly MJ, Devlin B, Roeder K, Sanders SJ, Talkowski ME. rare coding variation provides insight into the genetic architecture and phenotypic context of autism. Nat. Genet. 54, 1320–1331 (2022).

pubmed: 35982160 pmcid: 9653013 doi: 10.1038/s41588-022-01104-0

Zhou, X. et al. Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. Nat. Genet. 54, 1305–1319 (2022).

pubmed: 35982159 pmcid: 9470534 doi: 10.1038/s41588-022-01148-2

Yuen, R. K. et al. Whole-genome sequencing of quartet families with autism spectrum disorder. Nat. Med. 21, 185–191 (2015).

pubmed: 25621899 doi: 10.1038/nm.3792

Martin, A. R. et al. PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat. Genet. 51, 1560–1565 (2019).

pubmed: 31676867 doi: 10.1038/s41588-019-0528-2

Sobreira, N., Schiettecatte, F., Valle, D. & Hamosh, A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum. Mutat. 36, 928–930 (2015).

pubmed: 26220891 pmcid: 4833888 doi: 10.1002/humu.22844

Jiao, Y., Robison, A. J., Bass, M. A. & Colbran, R. J. Developmentally regulated alternative splicing of densin modulates protein-protein interaction and subcellular localization. J. Neurochem. 105, 1746–1760 (2008).

pubmed: 18248607 pmcid: 2814316 doi: 10.1111/j.1471-4159.2008.05280.x

Witte, H., Schreiner, D. & Scheiffele, P. A Sam68-dependent alternative splicing program shapes postsynaptic protein complexes. Eur. J. Neurosci. 49, 1436–1453 (2019).

pubmed: 30589479 pmcid: 6690840 doi: 10.1111/ejn.14332

Klein, S. A., Majumdar, A. & Barrick, D. A second backbone: the contribution of a buried asparagine ladder to the global and local stability of a leucine-rich repeat protein. Biochemistry. 58, 3480–3493 (2019).

pubmed: 31347358 doi: 10.1021/acs.biochem.9b00355

Wang, S. et al. A high-content imaging approach to profile C. elegans embryonic development. Development 146, 174029 (2019).

Labouesse, M. Epithelial junctions and attachments. WormBook 1–21 (2006).

Koppen, M. et al. Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia. Nat. Cell Biol. 3, 983–991 (2001).

pubmed: 11715019 doi: 10.1038/ncb1101-983

Ozden, C. et al. CaMKII binds both substrates and activators at the active site. Cell Rep. 40, 111064 (2022).

pubmed: 35830796 pmcid: 9336311 doi: 10.1016/j.celrep.2022.111064

Troyanovsky, R. B., Indra, I., Kato, R., Mitchell, B. J. & Troyanovsky, S. M. Basolateral protein Scribble binds phosphatase PP1 to establish a signaling network maintaining apicobasal polarity. J. Biol. Chem. 297, 101289 (2021).

pubmed: 34634305 pmcid: 8569552 doi: 10.1016/j.jbc.2021.101289

Bourgeron, T. A synaptic trek to autism. Curr. Opin. Neurobiol. 19, 231–234 (2009).

pubmed: 19545994 doi: 10.1016/j.conb.2009.06.003

Bonaglia, M. C. et al. Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. J. Med. Genet. 43, 822–828 (2006).

pubmed: 16284256 doi: 10.1136/jmg.2005.038604

Mick, E. et al. Genome-wide association study of the child behavior checklist dysregulation profile. J. Am. Acad. Child Adolesc. Psychiatry. 50, 807–17 e8 (2011).

pubmed: 21784300 pmcid: 3143361 doi: 10.1016/j.jaac.2011.05.001

Dobyns, W. B. et al. University of Washington Center for Mendelian G, Center for Mendelian Genomics at the Broad Institute of MIT, Harvard, Engle EC, Verheijen FW, Doherty D, Mancini GMS. MACF1 mutations encoding highly conserved zinc-binding residues of the gar domain cause defects in neuronal migration and axon guidance. Am. J. Hum. Genet. 103, 1009–1021 (2018).

pubmed: 30471716 pmcid: 6288423 doi: 10.1016/j.ajhg.2018.10.019

Ouimet, C. C., da Cruz e Silva, E. F. & Greengard, P. The alpha and gamma 1 isoforms of protein phosphatase 1 are highly and specifically concentrated in dendritic spines. Proc. Natl Acad. Sci. USA 92, 3396–3400 (1995).

pubmed: 7724573 pmcid: 42173 doi: 10.1073/pnas.92.8.3396

Uezu, A. et al. Identification of an elaborate complex mediating postsynaptic inhibition. Science. 353, 1123–1129 (2016).

pubmed: 27609886 pmcid: 5432043 doi: 10.1126/science.aag0821

Choy, M. S. et al. SDS22 selectively recognizes and traps metal-deficient inactive PP1. Proc. Natl Acad. Sci. USA 116, 20472–20481 (2019).

pubmed: 31548429 pmcid: 6789808 doi: 10.1073/pnas.1908718116

Bonsor, D. A. et al. Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome. Nat. Struct. Mol. Biol. 29, 966–977 (2022).

pubmed: 36175670 pmcid: 10365013 doi: 10.1038/s41594-022-00841-4

Kwon, J. J. et al. Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. Nature. 609, 408–415 (2022).

pubmed: 35831509 pmcid: 9694338 doi: 10.1038/s41586-022-04928-2

Hauseman, Z. J. et al. Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature. 609, 416–423 (2022).

pubmed: 35830882 pmcid: 9452295 doi: 10.1038/s41586-022-05086-1

Liau, N. P. D. et al. Structural basis for SHOC2 modulation of RAS signalling. Nature. 609, 400–407 (2022).

pubmed: 35768504 pmcid: 9452301 doi: 10.1038/s41586-022-04838-3

Foley, K., McKee, C., Nairn, A. C. & Xia, H. Regulation of synaptic transmission and plasticity by protein phosphatase 1. J. Neurosci. 41, 3040–3050 (2021).

pubmed: 33827970 pmcid: 8026358 doi: 10.1523/JNEUROSCI.2026-20.2021

Cai, Q. et al. CaMKIIalpha-driven, phosphatase-checked postsynaptic plasticity via phase separation. Cell Res. 31, 37–51 (2021).

pubmed: 33235361 doi: 10.1038/s41422-020-00439-9

Perfitt, T. L. et al. Neuronal L-Type calcium channel signaling to the nucleus requires a novel camkiialpha-shank3 interaction. J. Neurosci. 40, 2000–2014 (2020).

pubmed: 32019829 pmcid: 7055140 doi: 10.1523/JNEUROSCI.0893-19.2020

Allen, P. B., Ouimet, C. C. & Greengard, P. Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic spines. Proc. Natl Acad. Sci. USA 94, 9956–9961 (1997).

pubmed: 9275233 pmcid: 23308 doi: 10.1073/pnas.94.18.9956

MacMillan, L. B. et al. Brain actin-associated protein phosphatase 1 holoenzymes containing spinophilin, neurabin, and selected catalytic subunit isoforms. J Biol. Chem. 274, 35845–35854 (1999).

pubmed: 10585469 doi: 10.1074/jbc.274.50.35845

Morishita, W. et al. Regulation of synaptic strength by protein phosphatase 1. Neuron. 32, 1133–1148 (2001).

pubmed: 11754843 doi: 10.1016/S0896-6273(01)00554-2

Coultrap, S. J. et al. Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection. Cell Rep. 6, 431–437 (2014).

pubmed: 24485660 pmcid: 3930569 doi: 10.1016/j.celrep.2014.01.005

Bear, M. F., Huber, K. M. & Warren, S. T. The mGluR theory of fragile X mental retardation. Trends Neurosci. 27, 370–377 (2004).

pubmed: 15219735 doi: 10.1016/j.tins.2004.04.009

Greene, D., BioResource, N., Richardson, S. & Turro, E. A fast association test for identifying pathogenic variants involved in rare diseases. Am. J. Hum. Genet. 101, 104–114 (2017).

pubmed: 28669401 pmcid: 5501869 doi: 10.1016/j.ajhg.2017.05.015

Shcheglovitov, A. et al. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature. 503, 267–271 (2013).

pubmed: 24132240 pmcid: 5559273 doi: 10.1038/nature12618

Kim, D. I. et al. An improved smaller biotin ligase for BioID proximity labeling. Mol. Biol. Cell 27, 1188–1196 (2016).

pubmed: 26912792 pmcid: 4831873 doi: 10.1091/mbc.E15-12-0844

Hassani Nia, F. et al. Targeting of delta-catenin to postsynaptic sites through interaction with the Shank3 N-terminus. Mol. Autism. 11, 85 (2020).

pubmed: 33115499 pmcid: 7592556 doi: 10.1186/s13229-020-00385-8

Soltau, M., Richter, D. & Kreienkamp, H.-J. The insulin receptor substrate IRSp53 links postsynaptic shank1 to the small G-protein cdc42. Mol. Cell. Neurosci. 21, 575–583 (2002).

pubmed: 12504591 doi: 10.1006/mcne.2002.1201

Arribere, J. A. et al. Efficient marker-free recovery of custom genetic modifications with CRISPR/Cas9 in Caenorhabditis elegans. Genetics. 198, 837–846 (2014).

pubmed: 25161212 pmcid: 4224173 doi: 10.1534/genetics.114.169730

Paix, A. et al. Scalable and versatile genome editing using linear DNAs with microhomology to Cas9 sites in Caenorhabditis elegans. Genetics. 198, 1347–1356 (2014).

pubmed: 25249454 pmcid: 4256755 doi: 10.1534/genetics.114.170423

Huang, H. et al. Undiagnosed diseases N, Pak SC, Brody SL, Schedl T. A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C. Proc. Natl Acad. Sci. USA 119, e2105228119 (2022).

Dejima, K. et al. An aneuploidy-free and structurally defined balancer chromosome toolkit for Caenorhabditis elegans. Cell Rep. 22, 232–241 (2018).

pubmed: 29298424 doi: 10.1016/j.celrep.2017.12.024

Hassani Nia F., Woike D., Kloth K., Kortum F., Kreienkamp H. J. Truncating mutations in SHANK3 associated with global developmental delay interfere with nuclear beta-catenin signaling. J. Neurochem.155, 250–263 (2020).

Kutzing M. K., Langhammer C. G., Luo V., Lakdawala H., Firestein B. L. Automated Sholl analysis of digitized neuronal morphology at multiple scales. J. Vis. Exp. 14, e2354 (2010).

Langhammer, C. G. et al. Automated Sholl analysis of digitized neuronal morphology at multiple scales: whole cell Sholl analysis versus Sholl analysis of arbor subregions. Cytometry. A. 77, 1160–1168 (2010).

pubmed: 20687200 pmcid: 4619108 doi: 10.1002/cyto.a.20954

Arshadi, C., Gunther, U., Eddison, M., Harrington, K. I. S. & Ferreira, T. A. SNT: a unifying toolbox for quantification of neuronal anatomy. Nat. Methods. 18, 374–377 (2021).

pubmed: 33795878 doi: 10.1038/s41592-021-01105-7

Ferreira, T. A. et al. Neuronal morphometry directly from bitmap images. Nat. Methods. 11, 982–984 (2014).

pubmed: 25264773 pmcid: 5271921 doi: 10.1038/nmeth.3125