| Annotated protein: | Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif serine/threonine-protein kinase 3) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (mPar-1c). Gene symbol: MARK1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q8VHJ5 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ MARK1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse assembly (GO:0150052) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Kwan V, et al. "DIXDC1 Phosphorylation and Control of Dendritic Morphology Are Impaired by Rare Genetic Variants" Cell Rep. 2016 Nov 8;17(7):1892-1904 PMID:27829159 |
| Figure(s): | Figure 3, 4 |
| Annotation description: | Figure 3d: MARK1 and PSD95 (DLG4) were enriched in PSD biochemical fractions from 1-month-old mouse brains. Figure 3: MARK1 phosphorylates DIXDC1 at serine 592/381 and co-localized with DIXDC1 in dendrites of cultured cortical neurons. Figure 6B: "Expression of hDIXDC1-V43M and -T612M in HEK293 cells results in a decrease in phosphorylation at DIXDC1 serine592 in the presence of MARK1" Figure 4, S4B: Phosphorylation of DIXDC1 isoforms by MARK1 regulates neuronal morphology. "We also examined whether phosphorylation of DIXDC1 was important for its localization in dendrites and spines. Cultured cortical neurons showed co-localization of GFP-tagged hDIXDC1-WT (isoforms 1 and 2) with PSD95 in the dendritic spines (Figures 4G and 4H). However, the hDIXDC1-S592A and -S381A phospho-mutants both exhibited a decrease in PSD95 co-localization, indicating DIXDC1 localization to spines was disrupted (Figures 4G and 4H). These results strongly indicate that phosphorylation of both DIXDC1 isoforms is critical for cortical dendrite and synapse formation." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Antibody (detection) Over-expression |
| Evidence tracking, Experiment Assay: | Western blot Biochemical fractionation (generic) Confocal |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| Additional literature: | "we show that PAR-1 depletion causes defects in spine morphogenesis in hippocampal neurons and that a critical level of PAR-1 kinase activity is important for this process. Interestingly, although PAR-1 is known to regulate microtubule dynamics through phosphorylating MAPs, depletion of PAR-1 did not grossly affect microtubule transport. Instead, we found that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95. We found that PAR-1 phosphorylates PSD-95 at Ser-561 and that mutating this site to alanine reduces spine formation." @ PMID:22807451 "we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA), through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1." @ PMID:25932647 |
| SynGO annotation ID: | 5218 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |