Rab26 controls secretory granule maturation and breakdown in Drosophila

Boda, Attila and Varga, Luca Petra and Nagy, Anikó Zsuzsanna and Szenci, Győző and Csizmadia, Tamás and Lőrincz, Péter and Juhász, Gábor (2023) Rab26 controls secretory granule maturation and breakdown in Drosophila. CELLULAR AND MOLECULAR LIFE SCIENCES, 80. No-24. ISSN 1420-682X

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Abstract

At the onset of Drosophila metamorphosis, plenty of secretory glue granules are released from salivary gland cells and the glue is deposited on the ventral side of the forming (pre)pupa to attach it to a dry surface. Prior to this, a poorly understood maturation process takes place during which secretory granules gradually grow via homotypic fusions, and their contents are reorganized. Here we show that the small GTPase Rab26 localizes to immature (smaller, non-acidic) glue granules and its presence prevents vesicle acidification. Rab26 mutation accelerates the maturation, acidification and release of these secretory vesicles as well as the lysosomal breakdown (crinophagy) of residual, non-released glue granules. Strikingly, loss of Mon1, an activator of the late endosomal and lysosomal fusion factor Rab7, results in Rab26 remaining associated even with the large glue granules and a concomitant defect in glue release, similar to the effects of Rab26 overexpression. Our data thus identify Rab26 as a key regulator of secretory vesicle maturation that promotes early steps (vesicle growth) and inhibits later steps (lysosomal transport, acidification, content reorganization, release, and breakdown), which is counteracted by Mon1.

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