GTPase-activating protein TBC1D5 coordinates with retromer to constrain synaptic growth by inhibiting BMP signaling

Zhou, Xiu; Gan, Guangming; Sun, Yichen; Ou, Mengzhu; Geng, Jianhua; Wang, Jing; Yang, Xi; Hu, Shu; Jia, Da; Xie, Wei; He, Haihuai

doi:10.1016/j.jgg.2022.11.009

Cited by 5 publications

(3 citation statements)

References 71 publications

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“…Inducing knockdown of either Rab6 or Rab11 in SCs expressing the GFP-GPI DCG marker led to a strong reduction in the number of DCGs present in SCs (Figs 7A–7D and S7A–S7C Fig ). Indeed, the vast majority of cells expressing the most potent RNAis, Rab6 -RNAi #1 and Rab11 -RNAi #1, which have both been used to suppress Rab expression in previous studies [ 42 , 29 ], had no DCGs. Alongside this reduction in DCG-containing compartments, significantly fewer non-acidic compartments were present and many of those remaining were marked by diffuse GFP ( Fig 7E and 7F ).…”

Section: Resultsmentioning

confidence: 99%

“…UAS-RNAi lines were sourced from the Bloomington Drosophila Stock Centre TRiP collection (BDSC; [ 55 ]) and Vienna Drosophila Resource Centre shRNA, GD and KK libraries (VDRC; [ 56 ]): rosy-RNAi as a control (BDSC; 44106; HMS02827; [ 34 ]); Arf1-RNAi #1 (VDRC; 23082; [ 40 ]) and #2 (VDRC; 103572; [ 40 ]); AP-1γ-RNAi (BDSC; 27533; JF02684; [ 41 ]); AP-1μ-RNAi (VDRC; 24017; [ 57 ]); AP-1σ-RNAi (VDRC; 107322); Rab6-RNAi #1 (BDSC; 35744; HMS01486; [ 42 ]) and #2 (BDSC; 27490; JF02640; [ 58 ]); Rab11-RNAi #1 (BDSC; 27730; JF02812; [ 29 ]) and #2 (VDRC; 108382; [ 59 , 29 ]). UAS-driven YFP-labelled versions of wild type and mutant Rab6 and Rab11 were also employed [ 43 ]: UAS-YFP-Rab6 (BDSC; 23251); UAS-YFP-Rab6 Q71A (CA; BDSC; 9776); UAS-YFP-Rab6 T26N (DN; BDSC; 23250); UAS-YFP-Rab11 (BDSC; 50782); UAS-YFP-Rab11 Q70L (CA; BDSC; 50783); UAS-YFP-Rab11 S25N (DN; BDSC; 23261).…”

Section: Methodsmentioning

confidence: 99%

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A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in Drosophila secondary cells

Wells,

Mendes,

Castellanos

et al. 2023

PLoS Genet

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Secretory cells in glands and the nervous system frequently package and store proteins destined for regulated secretion in dense-core granules (DCGs), which disperse when released from the cell surface. Despite the relevance of this dynamic process to diseases such as diabetes and human neurodegenerative disorders, our mechanistic understanding is relatively limited, because of the lack of good cell models to follow the nanoscale events involved. Here, we employ the prostate-like secondary cells (SCs) of the Drosophila male accessory gland to dissect the cell biology and genetics of DCG biogenesis. These cells contain unusually enlarged DCGs, which are assembled in compartments that also form secreted nanovesicles called exosomes. We demonstrate that known conserved regulators of DCG biogenesis, including the small G-protein Arf1 and the coatomer complex AP-1, play key roles in making SC DCGs. Using real-time imaging, we find that the aggregation events driving DCG biogenesis are accompanied by a change in the membrane-associated small Rab GTPases which are major regulators of membrane and protein trafficking in the secretory and endosomal systems. Indeed, a transition from trans-Golgi Rab6 to recycling endosomal protein Rab11, which requires conserved DCG regulators like AP-1, is essential for DCG and exosome biogenesis. Our data allow us to develop a model for DCG biogenesis that brings together several previously disparate observations concerning this process and highlights the importance of communication between the secretory and endosomal systems in controlling regulated secretion.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in Drosophila secondary cells

Wells,

Mendes,

Castellanos

et al. 2023

PLoS Genet

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show abstract

“…TEM was performed according to the procedure described in our previous paper (Guangming et al, 2022;Zhou et al, 2023). In brief, wandering third-instar larvae were dissected in ice-cold disks in Jan solution (128 mM NaCl, 2 mM KCl, 4 mM MgCl 2 , 35 mM sucrose, 5 mM HEPES, pH 7.4) using standard techniques and then fixed with a mixed fixative containing 2% glutaraldehyde and 2% formaldehyde (dissolved in 0.1 M sodium cacodylate buffer, pH 7.4) at 4°C overnight.…”

Section: Transmission Electron Microscopy Analysis Of Larval Nmj Boutonsmentioning

confidence: 99%

Neurexin and neuroligins jointly regulate synaptic degeneration at the Drosophila neuromuscular junction based on TEM studies

Guangming,

Mei,

Qinfeng

et al. 2023

Front. Cell. Neurosci.

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The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development. Here, we show synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies. When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and the residual SSR then degenerates into a disordered, thin or linear membrane. The axon terminal begins to degenerate from the central region, and the T-bar detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons degenerate into a linear shape, and all the residual elements in axon terminals degenerate and eventually form a cluster of dark ultrafine particles. Swelling and retraction of the SSR occurs prior to degradation of the axon terminal, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in Drosophila neurexin (dnrx) dnrx273, Drosophila neuroligin (dnlg) dnlg1 and dnlg4 mutants and dnrx83;dnlg3 and dnlg2;dnlg3 double mutants, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration.

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Neurons Specialize in Presynaptic Autophagy: A Perspective to Ameliorate Neurodegeneration

Mishra,

Tripathi,

Kumar

et al. 2024

Mol Neurobiol

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GTPase-activating protein TBC1D5 coordinates with retromer to constrain synaptic growth by inhibiting BMP signaling

Cited by 5 publications

References 71 publications

A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in Drosophila secondary cells

A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in Drosophila secondary cells

Neurexin and neuroligins jointly regulate synaptic degeneration at the Drosophila neuromuscular junction based on TEM studies

Neurons Specialize in Presynaptic Autophagy: A Perspective to Ameliorate Neurodegeneration

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