Universität zu Köln

Kronenberg, Nils M., Tilston-Lunel, Andrew, Thompson, Frances E., Chen, Doris, Yu, Wanjia, Dholakia, Kishan, Gather, Malte C. ORCID: 0000-0002-4857-5562 and Gunn-Moore, Frank J. (2020). Willin/FRMD6 Influences Mechanical Phenotype and Neuronal Differentiation in Mammalian Cells by Regulating ERK1/2 Activity. Front. Cell. Neurosci., 14. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-5102

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Abstract

Willin/FRMD6 is part of a family of proteins with a 4.1 ezrin-radixin-moesin (FERM) domain. It has been identified as an upstream activator of the Hippo pathway and, when aberrant in its expression, is associated with human diseases and disorders. Even though Willin/FRMD6 was originally discovered in the rat sciatic nerve, most studies have focused on its functional roles in cells outside of the nervous system, where Willin/FRMD6 is involved in the formation of apical junctional cell-cell complexes and in regulating cell migration. Here, we investigate the biochemical and biophysical role of Willin/FRMD6 in neuronal cells, employing the commonly used SH-SY5Y neuronal model cell system and combining biochemical measurements with Elastic Resonator Interference Stress Micropscopy (ERISM). We present the first direct evidence that Willin/FRMD6 expression influences both the cell mechanical phenotype and neuronal differentiation. By investigating cells with increased and decreased Willin/FRMD6 expression levels, we show that Willin/FRMD6 not only affects proliferation and migration capacity of cells but also leads to changes in cell morphology and an enhanced formation of neurite-like membrane extensions. These changes were accompanied by alterations of biophysical parameters such as cell force, the organization of actin stress fibers and the formation of focal adhesions. At the biochemical level, changes in Willin/FRMD6 expression inversely affected the activity of the extracellular signal-regulated kinases (ERK) pathway and downstream transcriptional factor NeuroD1, which seems to prime SH-SY5Y cells for retinoic acid (RA)-induced neuronal differentiation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kronenberg, Nils M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tilston-Lunel, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Thompson, Frances E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Yu, Wanjia UNSPECIFIED UNSPECIFIED UNSPECIFIED Dholakia, Kishan UNSPECIFIED UNSPECIFIED UNSPECIFIED Gather, Malte C. UNSPECIFIED orcid.org/0000-0002-4857-5562 UNSPECIFIED Gunn-Moore, Frank J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-319739
DOI:	10.3389/fncel.2020.552213
Journal or Publication Title:	Front. Cell. Neurosci.
Volume:	14
Date:	2020
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1662-5102
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Physical Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETINOIC ACID; NEUROTROPHIC FACTOR; SIGNALING PATHWAY; ACTIVATION; PROTEIN; YAP; UPSTREAM; FAMILY Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/31973