Rab11 facilitates crosstalk between autophagy and endosomal pathway through regulation of Hook localization.

Szatmári, Zsuzsanna and Kis, Viktor and Lippai, Mónika and Hegedűs, Krisztina and Faragó, Tamás and Lőrincz, Péter and Juhász, Gábor and Sass, Miklós (2014) Rab11 facilitates crosstalk between autophagy and endosomal pathway through regulation of Hook localization. MOLECULAR BIOLOGY OF THE CELL, 25 (4). pp. 522-31. ISSN 1059-1524

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Abstract

During autophagy, double-membrane autophagosomes deliver sequestered cytoplasmic content to late endosomes and lysosomes for degradation. The molecular mechanism of autophagosome maturation is still poorly characterized. The small GTPase Rab11 regulates endosomal traffic, and is thought to function at the level of recycling endosomes. Here we show that loss of Rab11 leads to accumulation of autophagosomes and late endosomes in Drosophila melanogaster. Rab11 translocates from recycling endosomes to autophagosomes in response to autophagy induction, and physically interacts with Hook, a negative regulator of endosome maturation. Hook anchors endosomes to microtubules, and we show that Rab11 facilitates the fusion of endosomes and autophagosomes by removing Hook from mature late endosomes and inhibiting its homodimerization. Thus, induction of autophagy appears to promote autophagic flux by increased convergence with the endosomal pathway.

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