| Annotated protein: | Kalirin (EC 2.7.11.1) (Huntingtin-associated protein-interacting protein) (PAM COOH-terminal interactor protein 10) (P-CIP10) (Protein Duo) (Serine/threonine-protein kinase with Dbl- and pleckstrin homology domain). Gene symbol: KALRN. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P97924 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ KALRN |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Xie Z, et al. "Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines" Neuron. 2007 Nov 21;56(4):640-56 PMID:18031682 |
| Figure(s): | Figs 6, 7 and 8 |
| Annotation description: | Background: authors show that kalirin is a CAMKII regulated protein that controls spine morphology and activity dependent insertion of and retention of AMPARs in the dendritic spine (Figs 3, 5, 6 and 7). Kalirin is shown to act (in part) via Rac1 signalling in spine remodelling (Fig.1, Fig 4). Fig 6 : siRNA abrogation of Kalirin-7 expression prevents accumulation of GluR1 in dendritic spines and coincides with decreased AMPAR mediated basal synaptic transmission in the siRNA treated cells. Kalirin-7's effect on GluR1 recruitment and spine morphology/maturation is abolished by blocking actin polymerisation with lantrunculin A, indicating the involvement of Rac1 in this process. Fig 7: Pre-treatment of neurons with the K7 peptide to block binding and phosphorylation/activation of Kalirin-7 to CamKII prevents activity-dependent recruitment of GluR1 into dendritic spines. This is supported by the data in Fig 8 using Kalirin 7 siRNA treated neurons in place of the K7 peptide. -------------- I suggest replacing the paragraphs below with the paragraphs preceding this sentence. Fig.5 and 7: "Kalirin-7 expression and spine localization are required for maintenance of mature spine morphology" Fig.6 and 7: "Kalirin-7 controls AMPA receptor maintenance and activity-dependent insertion in spines" - "Altogether, these data provide evidence that kalirin regulates the insertion/maintenance of AMPARs at the synapse and AMPAR-mediated synaptic transmission" Background: authors show that kalirin is a CAMKII regulated protein that controls spine morphology and the retention of AMPARs in the dendritic spine (Fig.2). Kalirin is shown to act (in part) via Rac1 signaling needed for spine remodeling (Fig.1). Fig.5: "Kalirin-7 expression and spine localization are required for maintenance of mature spine morphology" Fig.6: "Kalirin-7 controls AMPA receptor maintenance in spines" - "Altogether, these data provide evidence that kalirin controls maintenance of AMPARs at the synapse and AMPAR-mediated synaptic transmission" - "These experiments strongly suggest that kalirin-7 promotes spine enlargement and GluR1 enrichment in spines by enhancing actin polymerization" Fig.7: "NMDAR-dependent spine delivery of AMPA receptors depends on CaMKII and kalirin spine targeting" Note: kalirin is shown to activate rac1 a known regulator of actin remodelling. In Fig.6 the authors use latrunculin an inhibitor of actin polymerization. Together this means that the effects on spine morphology and AMPAR localization are downstream of Rac1->actin This is captured in the final implementation: 'regulation of modification of postsynaptic actin cytoskeleton (GO:1905274)' regulates 'neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645)' |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp |
| Annotator(s): | John Chua (ORCID:0000-0002-5615-1014) |
| Lab: | Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Neurobiology/Ageing Program, Life Sciences Institute, National University of Singapore and Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore |
| SynGO annotation ID: | 2101 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |