KDEL Receptor Regulates Secretion by Lysosome Relocation- and Autophagy-dependent Modulation of Lipid-droplet Turnover

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Feb 15

PMID 30760704

Citations 29

Authors

Diego Tapia

Tomas Jimenez

Constanza Zamora

Javier Espinoza

Riccardo Rizzo

Alexis Gonzalez-Cardenas

Danitza Fuentes

Sergio Hernandez

Viviana A Cavieres

Andrea Soza

Fanny Guzman

Gloria Arriagada

Maria Isabel Yuseff

Gonzalo A Mardones

Patricia V Burgos

Alberto Luini

Alfonso Gonzalez

Jorge Cancino

Affiliations

Soon will be listed here.

Abstract

Inter-organelle signalling has essential roles in cell physiology encompassing cell metabolism, aging and temporal adaptation to external and internal perturbations. How such signalling coordinates different organelle functions within adaptive responses remains unknown. Membrane traffic is a fundamental process in which membrane fluxes need to be sensed for the adjustment of cellular requirements and homeostasis. Studying endoplasmic reticulum-to-Golgi trafficking, we found that Golgi-based, KDEL receptor-dependent signalling promotes lysosome repositioning to the perinuclear area, involving a complex process intertwined to autophagy, lipid-droplet turnover and Golgi-mediated secretion that engages the microtubule motor protein dynein-LRB1 and the autophagy cargo receptor p62/SQSTM1. This process, here named 'traffic-induced degradation response for secretion' (TIDeRS) discloses a cellular mechanism by which nutrient and membrane sensing machineries cooperate to sustain Golgi-dependent protein secretion.

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References

Sontag E . Some new directions in control theory inspired by systems biology. Syst Biol (Stevenage). 2006; 1(1):9-18. DOI: 10.1049/sb:20045006. View

Gordon D, Bond L, Sahlender D, Peden A . A targeted siRNA screen to identify SNAREs required for constitutive secretion in mammalian cells. Traffic. 2010; 11(9):1191-204. DOI: 10.1111/j.1600-0854.2010.01087.x. View

Xie Z, Nair U, Klionsky D . Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell. 2008; 19(8):3290-8. PMC: 2488302. DOI: 10.1091/mbc.e07-12-1292. View

Gonzalez A, Munoz V, Cavieres V, Bustamante H, Cornejo V, Januario Y . Autophagosomes cooperate in the degradation of intracellular C-terminal fragments of the amyloid precursor protein the MVB/lysosomal pathway. FASEB J. 2017; 31(6):2446-2459. DOI: 10.1096/fj.201600713R. View

Kitano H . Towards a theory of biological robustness. Mol Syst Biol. 2007; 3:137. PMC: 2013924. DOI: 10.1038/msb4100179. View

De Matteis M, Rega L . Endoplasmic reticulum-Golgi complex membrane contact sites. Curr Opin Cell Biol. 2015; 35:43-50. DOI: 10.1016/j.ceb.2015.04.001. View

Valm A, Cohen S, Legant W, Melunis J, Hershberg U, Wait E . Applying systems-level spectral imaging and analysis to reveal the organelle interactome. Nature. 2017; 546(7656):162-167. PMC: 5536967. DOI: 10.1038/nature22369. View

Prudent J, McBride H . The mitochondria-endoplasmic reticulum contact sites: a signalling platform for cell death. Curr Opin Cell Biol. 2017; 47:52-63. DOI: 10.1016/j.ceb.2017.03.007. View

Bar-Peled L, Schweitzer L, Zoncu R, Sabatini D . Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell. 2012; 150(6):1196-208. PMC: 3517996. DOI: 10.1016/j.cell.2012.07.032. View

10.

Rizzo R, Parashuraman S, Mirabelli P, Puri C, Lucocq J, Luini A . The dynamics of engineered resident proteins in the mammalian Golgi complex relies on cisternal maturation. J Cell Biol. 2013; 201(7):1027-36. PMC: 3691466. DOI: 10.1083/jcb.201211147. View

11.

Giannotta M, Ruggiero C, Grossi M, Cancino J, Capitani M, Pulvirenti T . The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi. EMBO J. 2012; 31(13):2869-81. PMC: 3395092. DOI: 10.1038/emboj.2012.134. View

12.

Herms A, Bosch M, Reddy B, Schieber N, Fajardo A, Ruperez C . AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation. Nat Commun. 2015; 6:7176. PMC: 4446796. DOI: 10.1038/ncomms8176. View

13.

Dakik P, Titorenko V . Communications between Mitochondria, the Nucleus, Vacuoles, Peroxisomes, the Endoplasmic Reticulum, the Plasma Membrane, Lipid Droplets, and the Cytosol during Yeast Chronological Aging. Front Genet. 2016; 7:177. PMC: 5037234. DOI: 10.3389/fgene.2016.00177. View

14.

Wang S, Tsun Z, Wolfson R, Shen K, Wyant G, Plovanich M . Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science. 2015; 347(6218):188-94. PMC: 4295826. DOI: 10.1126/science.1257132. View

15.

Tatsumi T, Takayama K, Ishii S, Yamamoto A, Hara T, Minami N . Forced lipophagy reveals that lipid droplets are required for early embryonic development in mouse. Development. 2018; 145(4). DOI: 10.1242/dev.161893. View

16.

Gordon D, Chia J, Jayawardena K, Antrobus R, Bard F, Peden A . VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane. PLoS Genet. 2017; 13(4):e1006698. PMC: 5406017. DOI: 10.1371/journal.pgen.1006698. View

17.

Wang P, Li B, Zhou L, Fei E, Wang G . The KDEL receptor induces autophagy to promote the clearance of neurodegenerative disease-related proteins. Neuroscience. 2011; 190:43-55. DOI: 10.1016/j.neuroscience.2011.06.008. View

18.

Sharma K, DSouza R, Tyanova S, Schaab C, Wisniewski J, Cox J . Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep. 2014; 8(5):1583-94. DOI: 10.1016/j.celrep.2014.07.036. View

19.

Jin Q, Zhong Y, Mulder K . Requirement for protein kinase A in the phosphorylation of the TGFβ receptor-interacting protein km23-1 as a component of TGFβ downstream effects. Exp Cell Res. 2013; 319(6):897-907. PMC: 3723345. DOI: 10.1016/j.yexcr.2012.12.029. View

20.

Solis G, Bilousov O, Koval A, Luchtenborg A, Lin C, Katanaev V . Golgi-Resident Gαo Promotes Protrusive Membrane Dynamics. Cell. 2017; 170(5):939-955.e24. DOI: 10.1016/j.cell.2017.07.015. View