Alternative titles; symbols
HGNC Approved Gene Symbol: SYNPO
Cytogenetic location: 5q33.1 Genomic coordinates (GRCh38) : 5:150,586,010-150,659,207 (from NCBI)
Synaptopodin is an actin-associated protein that may play a role in actin-based cell shape and motility. The name synaptopodin derives from the protein's associations with postsynaptic densities and dendritic spines and with renal podocytes (Mundel et al., 1997).
By searching an EST database for sequences similar to tryptic fragments of rat synaptopodin, followed by RT-PCR of a human hippocampus cDNA library, Mundel et al. (1997) cloned full-length SYNPO. The deduced 685-amino acid protein has a calculated molecular mass of 73.7 kD. Mundel et al. (1997) also cloned mouse synaptopodin, which encodes a 690-amino acid protein with a calculated molecular mass of about 74 kD. Mouse and human SYNPO share 84% amino acid identity. SYNPO contains a high proline content (20%), making it unlikely that SYNPO forms a globular domain. It has several potential phosphorylation sites and 2 PPxY motifs, which interact with WW domain proteins. Northern blot analysis of human cerebral cortex detected a 4.4-kb transcript. Western blot analysis detected synaptopodin in rat brain beginning at embryonic day 15, with maximal expression in adult animals. In situ hybridization detected mouse synaptopodin in perikarya of the olfactory bulb, cerebral cortex, striatum, and hippocampus. Immunolocalization of cultured rat hippocampal neurons detected synaptopodin colocalized with synaptophysin (313475) in a dotted pattern along dendrites. Synaptopodin was not detected in mouse renal podocyte precursor cells that showed epithelial morphology, but upon differentiation to podocytes, synaptopodin was observed in a dotted pattern along actin microfilaments and colocalized with vinculin (193065) at focal contacts.
By sequencing clones obtained from a fetal brain cDNA library, Kikuno et al. (1999) cloned SYNPO, which they designated KIAA1029. The 3-prime untranslated region contains an Alu repeat, and the deduced protein contains 903 amino acids. RT-PCR ELISA detected very high expression in ovary and high expression in spinal cord, skeletal muscle, heart, lung, liver, and kidney. Low expression was detected in all other tissues examined, including whole adult brain, and very low expression was detected in fetal brain. Low to moderate expression was detected in all specific adult brain regions examined, with highest expression in amygdala.
Asanuma et al. (2005) noted 3 isoforms of synaptopodin, Synpo-long (903 amino acids), Synpo-short (685 amino acids), and a so-called Synpo-T form (181 amino acids) that is identical to the C terminus of Synpo-long. Using immunofluorescence microscopy, they demonstrated that Synpo-long is expressed in the kidney and Synpo-short in the brain.
By yeast 2-hybrid assay, in vitro binding assays, and immunoprecipitation of transfected human embryonic kidney cells, Patrie et al. (2002) determined that the second WW domain of mouse Magi1 (BAIAP1; 602625) interacted with human synaptopodin. They also found that exogenously expressed human synaptopodin and rat alpha-actinin-4 (604638) colocalized with endogenous Magi1 at tight junctions of canine kidney epithelial cells.
In cotransfection experiments in human embryonic kidney cells, Asanuma et al. (2005) demonstrated that synaptopodin bundles and elongates alpha-actinin-induced actin filaments in an isoform-specific manner.
The International Radiation Hybrid Mapping Consortium mapped the SYNPO gene to chromosome 5 (stSG26867).
Deller et al. (2003) reported that mice homozygous for targeted deletion of the Synpo gene completely lacked dendritic spine apparatuses. The absence of dendritic spine apparatuses was accompanied by a reduction in long-term potentiation in the CA1 region of the hippocampus and by impaired spatial learning in a maze test.
Asanuma et al. (2005) found that despite the ultrastructurally normal appearance of their podocytes, Synpo -/- mice displayed impaired recovery from protamine sulfate-induced podocyte foot process effacement and from lipopolysaccharide-induced nephrotic syndrome, and that Synpo -/- podocytes showed impaired actin filament reformation in vitro. The authors noted that Synpo -/- mice lacked expression of the Synpo-long and Synpo-short isoforms, but showed upregulation of Synpo-T in podocytes; gene silencing of Synpo-T abrogated stress fiber formation in Synpo -/- podocytes. Asanuma et al. (2005) concluded that Synpo-T serves as a backup for Synpo-long in Synpo -/- podocytes.
Asanuma, K., Kim, K., Oh, J., Giardino, L., Chabanis, S., Faul, C., Reiser, J., Mundel, P. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J. Clin. Invest. 115: 1188-1198, 2005. Note: Erratum: J. Clin. Invest. 122: 781 only, 2012. [PubMed: 15841212] [Full Text: https://doi.org/10.1172/JCI23371]
Deller, T., Korte, M., Chabanis, S., Drakew, A., Schwegler, H., Stefani, G. G., Zuniga, A., Schwarz, K., Bonhoeffer, T., Zeller, R., Frotscher, M., Mundel, P. Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity. Proc. Nat. Acad. Sci. 100: 10494-10499, 2003. [PubMed: 12928494] [Full Text: https://doi.org/10.1073/pnas.1832384100]
Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 197-205, 1999. [PubMed: 10470851] [Full Text: https://doi.org/10.1093/dnares/6.3.197]
Mundel, P., Heid, H. W., Mundel, T. M., Kruger, M., Reiser, J., Kriz, W. Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes. J. Cell Biol. 139: 193-204, 1997. [PubMed: 9314539] [Full Text: https://doi.org/10.1083/jcb.139.1.193]
Patrie, K. M., Drescher, A. J., Welihinda, A., Mundel, P., Margolis, B. Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1. J. Biol. Chem. 277: 30183-30190, 2002. [PubMed: 12042308] [Full Text: https://doi.org/10.1074/jbc.M203072200]