Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.575227
Keywords
syndecan-4; proteoglycan; cell polarity; super-resolution microscopy; actin; calcium; centrosome; cell migration
Categories
Funding
- National Research, Development and Innovation Office of Hungary [GINOP-2.3.2-15-2016-00040, EFOP-3.6.2-16-2017-00006, NKFI FK 134684, NKFI K 132446, GINOP-2.3.2-15-2016-00036]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences
- New National Excellence Program of the Ministry for Innovation and Technology Sciences [UNKP-19-4-SZTE-23]
- National Research, Development and Innovation Fund [OTKA_K 128123]
- Szeged Scientists Academy under Hungarian Ministry of Human Capacities [EMMI:13725-2/2018/INTFIN]
- Hungarian Brain Research Programme [2017-1.2.1-NKP-2017-00002]
- EU [EFOP-3.6.1-16-2016-00008]
- LENDULET-BIOMAG Grant [2018-342]
- European Regional Development Funds [GINOP-2.3.2-15-2016-00006, GINOP-2.3.2-15-2016-00026, GINOP-2.3.2-15-2016-00037]
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Efficient cell migration requires cellular polarization, which is characterized by the formation of leading and trailing edges, appropriate positioning of the nucleus and reorientation of the Golgi apparatus and centrosomes toward the leading edge. Migration also requires the development of an asymmetrical front-to-rear calcium (Ca2+) gradient to regulate focal adhesion assembly and actomyosin contractility. Here we demonstrate that silencing of syndecan-4, a transmembrane heparan sulfate proteoglycan, interferes with the correct polarization of migrating mammalian myoblasts (i.e., activated satellite stem cells). In particular, syndecan-4 knockdown completely abolished the intracellular Ca2+ gradient, abrogated centrosome reorientation and thus decreased cell motility, demonstrating the role of syndecan-4 in cell polarity. Additionally, syndecan-4 exhibited a polarized distribution during migration. Syndecan-4 knockdown cells exhibited decreases in the total movement distance during directional migration, maximum and vectorial distances from the starting point, as well as average and maximum cell speeds. Super-resolution direct stochastic optical reconstruction microscopy images of syndecan-4 knockdown cells revealed nanoscale changes in the actin cytoskeletal architecture, such as decreases in the numbers of branches and individual branch lengths in the lamellipodia of the migrating cells. Given the crucial importance of myoblast migration during embryonic development and postnatal muscle regeneration, we conclude that our results could facilitate an understanding of these processes and the general role of syndecan-4 during cell migration.
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