» Articles » PMID: 38201288

Synaptopodin-2 Isoforms Have Specific Binding Partners and Display Distinct, Muscle Cell Type-Specific Expression Patterns

Abstract

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology.

Citing Articles

Bone marrow mesenchymal stem cells alleviate neurological dysfunction by reducing autophagy damage via downregulation of SYNPO2 in neonatal hypoxic-ischemic encephalopathy rats.

Xue L, Cheng J, Du R, Luo B, Chen L, Xiao Q Cell Death Dis. 2025; 16(1):131.

PMID: 40000609 PMC: 11862179. DOI: 10.1038/s41419-025-07439-w.


Comparison of genomic prediction accuracy using different models for egg production traits in Taiwan country chicken.

Tu T, Lin C, Liu M, Hsu Z, Chen C Poult Sci. 2024; 103(10):104063.

PMID: 39098301 PMC: 11639322. DOI: 10.1016/j.psj.2024.104063.

References
1.
De Ganck A, De Corte V, Staes A, Gevaert K, Vandekerckhove J, Gettemans J . Multiple isoforms of the tumor suppressor myopodin are simultaneously transcribed in cancer cells. Biochem Biophys Res Commun. 2008; 370(2):269-73. DOI: 10.1016/j.bbrc.2008.03.086. View

2.
Leinweber B, Fredricksen R, Hoffman D, Chalovich J . Fesselin: a novel synaptopodin-like actin binding protein from muscle tissue. J Muscle Res Cell Motil. 1999; 20(5-6):539-45. DOI: 10.1023/a:1005597306671. View

3.
Renegar R, Chalovich J, Leinweber B, Zary J, Schroeter M . Localization of the actin-binding protein fesselin in chicken smooth muscle. Histochem Cell Biol. 2008; 131(2):191-6. PMC: 3832296. DOI: 10.1007/s00418-008-0508-6. View

4.
Weins A, Schwarz K, Faul C, Barisoni L, Linke W, Mundel P . Differentiation- and stress-dependent nuclear cytoplasmic redistribution of myopodin, a novel actin-bundling protein. J Cell Biol. 2001; 155(3):393-404. PMC: 2150840. DOI: 10.1083/jcb.200012039. View

5.
Zheng Z, Song Y . Synaptopodin-2: a potential tumor suppressor. Cancer Cell Int. 2023; 23(1):158. PMC: 10405370. DOI: 10.1186/s12935-023-03013-6. View