Universität zu Köln

Negrete-Hurtado, A., Overhoff, M., Bera, S., De Bruyckere, E., Schaetzmueller, K., Kye, M. J., Qin, C., Lammers, M., Kondylis, V., Neundorf, I. ORCID: 0000-0001-6450-3991 and Kononenko, N. L. (2020). Autophagy lipidation machinery regulates axonal microtubule dynamics but is dispensable for survival of mammalian neurons. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Neurons maintain axonal homeostasis via employing a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Abnormal MT-based trafficking hallmarks the pathology of neurodegenerative diseases, but the exact mechanism regulating MT dynamics in axons remains enigmatic. Here we report on a regulation of MT dynamics by AuTophaGy(ATG)-related proteins, which previously have been linked to the autophagy pathway. We find that ATG proteins required for LC3 lipid conjugation are dispensable for survival of excitatory neurons and instead regulate MT stability via controlling the abundance of the MT-binding protein CLASP2. This function of ATGs is independent of their role in autophagy and requires the active zone protein ELKS1. Our results highlight a non-canonical role of ATG proteins in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of cytoplasmic material, but also impair axonal integrity via altering MT stability.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Negrete-Hurtado, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Overhoff, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bera, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED De Bruyckere, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaetzmueller, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kye, M. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Qin, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lammers, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kondylis, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, I. UNSPECIFIED orcid.org/0000-0001-6450-3991 UNSPECIFIED Kononenko, N. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-340321
DOI:	10.1038/s41467-020-15287-9
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEURODEGENERATIVE DISEASE; SYNAPTIC BOUTONS; PROTEIN; TUBULIN; PATHOGENESIS; COMPLEX; MECHANISMS; REQUIRES; PATTERNS; CLASPS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/34032