Investigating protein networks and mechanisms that regulate protein trafficking, signalling and organelle function

The Apaja group are investigating the protein networks and molecular mechanisms that regulate membrane trafficking and proteostasis in human cells.

An important aspect is to gain a molecular-level understanding of how cellular stress responses change membrane organelle function, protein degradation, pH and calcium regulation and signalling events including ubiquitin signalling. The combined dynamics regulate proteostasis and is monitored by protein quality control machinery.

  • Ubiquitin signalling and dynamics in proteostasis regulation and membrane trafficking in human disease.
  • Protein networks that regulate cargo sorting especially at the lysosome-autophagy pathway.
  • Functional interaction networks modulating proteostasis by cellular stress responses; organelle proteomics and effect of pH and calcium regulation.
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Kazan JM, Lukacs GL, Apaja PM, Pause A

ESCRT Complexes: Methods Mol Biol. (2019) 1998:93-103. 

Okiyoneda T, Veit G, Sakai R, Aki M, Fujihara T, Higashi M, Susuki-Miyata S, Miyata M, Fukuda N, Yoshida A, Xu H, Apaja PM, Lukacs GL (2018)

Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase

Dev Cell. 44(6):694-708.e7. doi: 10.1016/j.devcel.2018.02.001. PMID:29503157.

Gaitán-Peñas H et al. (2017)

Leukoencephalopathy-causing CLCN2 mutations are associated with impaired Cl channel function and trafficking.

J Physiol. 595(22), 6993-7008.

Veit G, Oliver K, Apaja PM, Perdomo D, Bidaud-Meynard A, Lin ST, Guo J, Icyuz M, Sorscher EJ, Hartman Iv JL, Lukacs GL.

Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.

PLoS Biol. 2016 May 11;14(5):e1002462. doi: 10.1371/journal.pbio.1002462. eCollection 2016 May.

Kharitidi D, Apaja PM, Manteghi S, Suzuki K, Malitskaya E, Roldan A, Gingras MC, Takagi J, Lukacs GL, Pause A.

Interplay of endosomal pH and ligand occupancy in integrin 51 ubiquitination, endocytic sorting and cell migration.

Cell Rep. 2015 Oct 20;13(3):599-609. doi: 10.1016/j.celrep.2015.09.024. Epub 2015 Oct 8.

Apaja PM and Lukacs GL.

Protein homeostasis at the plasma membrane.

Physiology (Bethesda). 2014 Jul;29(4):265–277. doi: 10.1152/physiol.00058.2013.

Veit G, Avramescu RG, Perdomo D, Phuan PW, Bagdany M, Apaja PM, Borot F, Szollosi D, Wu YS, Finkbeiner WE, Hegedus T, Verkman AS, Lukacs GL.

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

Sci Transl Med. 2014 Jul 23;6(246):246ra97. doi: 10.1126/scitranslmed.3008889.

Chu CY, King J, Berrini M, Rumley AC, Apaja PM, Lukacs GL, Alexander RT, Cordat E.

Degradation mechanism of a Golgi-retained distal renal tubular acidosis mutant of the kidney anion exchanger 1 in renal cells.

Am J Physiol Cell Physiol. 2014 Aug 1;307(3):C296-307. doi: 10.1152/ajpcell.00310.2013. Epub 2014 Jun 11.

Okiyoneda T, Apaja PM and Lukacs GL.

Protein quality control at the plasma membrane.

Curr Opin Cell Biol. 2011 Aug;23(4):483-91. doi: 10.1016/j.ceb.2011.04.012. Epub 2011 May 14.

Apaja PM et al. (2010)

Quality control for unfolded proteins at the plasma membrane.

J Cell Biol. 191(3), 533-70.