Universität zu Köln

Kononenko, Natalia L., Classen, Gala A., Kuijpers, Marijn, Puchkov, Dmytro ORCID: 0000-0001-8341-4847, Maritzen, Tanja ORCID: 0000-0003-4993-0340, Tempes, Aleksandra, Malik, Anna R., Skalecka, Agnieszka, Bera, Sujoy, Jaworski, Jacek ORCID: 0000-0001-8760-7865 and Haucke, Volker (2017). Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Autophagosomes primarily mediate turnover of cytoplasmic proteins or organelles to provide nutrients and eliminate damaged proteins. In neurons, autophagosomes form in distal axons and are trafficked retrogradely to fuse with lysosomes in the soma. Although defective neuronal autophagy is associated with neurodegeneration, the function of neuronal autophagosomes remains incompletely understood. We show that in neurons, autophagosomes promote neuronal complexity and prevent neurodegeneration in vivo via retrograde transport of brain-derived neurotrophic factor (BDNF)-activated TrkB receptors. p150Glued/dynactin-dependent transport of TrkB-containing autophagosomes requires their association with the endocytic adaptor AP-2, an essential protein complex previously thought to function exclusively in clathrin-mediated endocytosis. These data highlight a novel non-canonical function of AP-2 in retrograde transport of BDNF/TrkB-containing autophagosomes in neurons and reveal a causative link between autophagy and BDNF/TrkB signalling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kononenko, Natalia L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Classen, Gala A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuijpers, Marijn UNSPECIFIED UNSPECIFIED UNSPECIFIED Puchkov, Dmytro UNSPECIFIED orcid.org/0000-0001-8341-4847 UNSPECIFIED Maritzen, Tanja UNSPECIFIED orcid.org/0000-0003-4993-0340 UNSPECIFIED Tempes, Aleksandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Malik, Anna R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Skalecka, Agnieszka UNSPECIFIED UNSPECIFIED UNSPECIFIED Bera, Sujoy UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaworski, Jacek UNSPECIFIED orcid.org/0000-0001-8760-7865 UNSPECIFIED Haucke, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-234089
DOI:	10.1038/ncomms14819
Journal or Publication Title:	Nat. Commun.
Volume:	8
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AXONAL-TRANSPORT; CORTICAL-NEURONS; TRANSCRIPTION FACTORS; SIGNALING ENDOSOMES; MAMMALIAN-CELLS; STONIN 2; DYNEIN; BDNF; SYSTEM; MICE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23408