Universität zu Köln

Walsh, Melissa B., Janzen, Eva, Wingrove, Emily, Hosseinibarkooie, Seyyedmohsen, Muela, Natalia Rodriguez, Davidow, Lance, Dimitriadi, Maria, Norabuena, Erika M., Rubin, Lee L., Wirth, Brunhilde and Hart, Anne C. (2020). Genetic modifiers ameliorate endocytic and neuromuscular defects in a model of spinal muscular atrophy. BMC Biol., 18 (1). LONDON: BMC. ISSN 1741-7007

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Abstract

Background Understanding the genetic modifiers of neurodegenerative diseases can provide insight into the mechanisms underlying these disorders. Here, we examine the relationship between the motor neuron disease spinal muscular atrophy (SMA), which is caused by reduced levels of the survival of motor neuron (SMN) protein, and the actin-bundling protein Plastin 3 (PLS3). Increased PLS3 levels suppress symptoms in a subset of SMA patients and ameliorate defects in SMA disease models, but the functional connection between PLS3 and SMN is poorly understood. Results We provide immunohistochemical and biochemical evidence for large protein complexes localized in vertebrate motor neuron processes that contain PLS3, SMN, and members of the hnRNP F/H family of proteins. Using aCaenorhabditis elegans(C. elegans) SMA model, we determine that overexpression of PLS3 or loss of theC. eleganshnRNP F/H ortholog SYM-2 enhances endocytic function and ameliorates neuromuscular defects caused by decreased SMN-1 levels. Furthermore, either increasing PLS3 or decreasing SYM-2 levels suppresses defects in aC. elegansALS model. Conclusions We propose that hnRNP F/H act in the same protein complex as PLS3 and SMN and that the function of this complex is critical for endocytic pathways, suggesting that hnRNP F/H proteins could be potential targets for therapy development.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walsh, Melissa B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Janzen, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Wingrove, Emily UNSPECIFIED UNSPECIFIED UNSPECIFIED Hosseinibarkooie, Seyyedmohsen UNSPECIFIED UNSPECIFIED UNSPECIFIED Muela, Natalia Rodriguez UNSPECIFIED UNSPECIFIED UNSPECIFIED Davidow, Lance UNSPECIFIED UNSPECIFIED UNSPECIFIED Dimitriadi, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Norabuena, Erika M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubin, Lee L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Brunhilde UNSPECIFIED UNSPECIFIED UNSPECIFIED Hart, Anne C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-319006
DOI:	10.1186/s12915-020-00845-w
Journal or Publication Title:	BMC Biol.
Volume:	18
Number:	1
Date:	2020
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1741-7007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SURVIVAL-MOTOR-NEURON; AMYOTROPHIC-LATERAL-SCLEROSIS; CAENORHABDITIS-ELEGANS; MESSENGER-RNA; SYNAPTIC-TRANSMISSION; FUNCTIONAL-ANALYSIS; PROTEIN COMPLEX; SMN PROTEIN; PLASTIN; LOCALIZATION Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31900