Autophagy generates retrogradely transported organelles: a hypothesis

Date

2008

Authors

Kaasinen, Selma
Hendry, Ian
Harvey, L
Reynolds, Anna J

Journal Title

Journal ISSN

Volume Title

Publisher

Pergamon-Elsevier Ltd

Abstract

Nerve cells require trophic signals transmitted from the nerve terminal via the axon in order to survive and develop normally. As the axon may be more than a meter long, specialised mechanisms are needed to transmit these signals. This involves the retrograde axonal transport of signalling endosomes containing nerve growth factor (NGF) and other synaptically derived molecules. These are large, double membrane multivesicular bodies containing a mixture of all vesicle types seen in the nerve terminal. How this signalling endosome is formed and targeted for retrograde axonal transport, however, remains an open question. Here we show that members of the Rab family of proteins that are retrogradely transported indicate that the signalling endosome contains both early and recycling endosomes. In addition, we show that retrogradely transported labelled antibody to dopamine beta-hydroxylase, a marker for synaptic vesicles, co-localizes within the same signalling endosome as NGF. We further show that LC3, a marker for autophagosomes, is retrogradely transported and associates with retrogradely transported NGF. We propose that neurons have exploited the mechanism of autophagy to engulf a sample of the cytoplasmic contents of the nerve terminal to transport back to the cell body. This sample of cytoplasmic contents relays a reliable snapshot of the totality of signalling events occurring in the nerve terminal at that instant in time.

Description

Keywords

Keywords: microtubule associated protein; nerve growth factor; animal tissue; article; autophagy; cell organelle; controlled study; hypothesis; nonhuman; priority journal; protein localization; rat; Animals; Autophagy; Axonal Transport; Biotinylation; Dopamine beta Autophagocytosis; Nerve growth factor; p75; Rab proteins; Receptor tyrosine kinase A; Signalling endosome

Citation

Source

International Journal of Developmental Neuroscience

Type

Journal article

Book Title

Entity type

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Restricted until

2037-12-31