The Apaja group are investigating the mechanisms that regulates protein trafficking and organelle function and their role in cellular homeostasis,  and  are unravelling how the endo-lysosomal network dysfunction leads to disease conditions such as neurological disorders and cancers.

Research

The group is focusing on discovering molecular networks that are responsible of protein trafficking at the endo-lysosome-autophagy system and mechanisms maintaining the healthy proteostasis in cells.

An important aspect is to gain molecular level understanding how changes in the organelle function contributes to the protein degradation, pH and calcium regulation and signalling events.   These combined dynamics regulate protein trafficking between organelles as well as their degradation or recycling at the endosomal pathway, and is a determinant factor in plasma membrane expression levels of membrane proteins. Thus, this balance is monitored by protein quality control machinery surveilling the protein conformers.

The group's aim is to discover mechanisms in organelle regulation in health and disease, and how to therapeutically interfere on organelle and protein trafficking diseases.  

 

  • Mechanisms regulating lysosome-autophagy homeostasis and contribution into some disease conditions
  • Dynamic ubiquitination process at the endosomal pathway and its role in vesicular cargo trafficking and signal transduction.
  • The development of methodology for detecting organelle proteomics and  their pH and calcium regulation, and methods for monitoring protein ubiquitination events.
  • Protein networks that regulate cargo sorting or mis-sorting to the lysosomes/autophagosomes

 

Authors
Title
Published In
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.