Universität zu Köln

Calculli, Giuseppe (2020). Germline cey proteins prevent protein aggregation in the soma of C. elegans. PhD thesis, Universität zu Köln.

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Abstract

Protein aggregation causes intracellular changes in neurons, that elicit signals to modulate proteostasis in the periphery. Beyond the nervous system, a fundamental question is whether other organs also communicate their proteostasis status to distal tissues. Here, we examined whether proteostasis of the germline influences somatic tissues. To this end, we induced aggregation of germline-specific PGL-1 protein in C. elegans germline stem cells. Notably, dysfunction of germline proteostasis triggered neuronal aggregation of distinct proteins linked with neurodegenerative diseases such as Huntington’s and amyotrophic lateral sclerosis. The cell non-autonomous effects induced by PGL-1 aggregation were not limited to the nervous system, affecting other tissues such as the muscle and intestine. Importantly, PGL-1 aggregation reduced the mitochondrial network of germline cells. In turn, these cells diminished the mitochondrial content, network and proteostasis of mitochondria in somatic tissues through Wnt/mitokine signaling, resulting in the aggregation of disease-related proteins. Thus, the proteostasis status of germline stem cells coordinates mitochondrial networks and protein aggregation through the organism.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Calculli, Giuseppe gcalcul1@uni-koeln.de UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-498719
Date:	4 June 2020
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Generalities, Science Natural sciences and mathematics
Uncontrolled Keywords:	Keywords Language UNSPECIFIED English
Date of oral exam:	24 February 2021
Referee:	Name Academic Title Trifunivic, Aleksandra Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/49871