Endosomal Dynamics in Health and Disease
My group is funded by an Emmy Noether Junior Research Fellowship of the German Research Council (DFG). We are interested and actively investigate all aspects of endosomal biology with a focus on the endosomal recycling system. Endosomes are highly dynamic vesicular and tubular organelles that transport internalized receptors, adhesion molecules or transporters through the interior of the cells to maintain their distribution across the cellular compartments. Impaired endosomal transport is increasingly recognized as a major contributor to many devastating pathologies such as Alzheimer’s disease or Parkinsonism, which makes it important to understand the function and molecular mechanisms governing the endosomal network.
To investigate how endosomes operate on a molecular level we employ tissue culture of mammalian cells, CRISPR-CAS9 based genome editing, state of the art quantitative proteomics as well as high resolution microscopy techniques. In particular, we use these methods to study proteins that reside on the cytosolic side of endosomes, such as sorting nexins (SNXs), Rab GTPases and an endosomal coat complex called the retromer complex.
SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways.
Steinberg F, Heesom KJ, Bass MD, Cullen PJ.
J Cell Biol. 2012 Apr 16;197(2):219-30. doi: 10.1083/jcb.201111121. Epub 2012 Apr 9.
A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport.
Steinberg F, Gallon M, Winfield M, Thomas EC, Bell AJ, Heesom KJ, Tavaré JM, Cullen PJ.
Nat Cell Biol. 2013 May
Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation.
McGough IJ, Steinberg F, Jia D, Barbuti PA, McMillan KJ, Heesom KJ, Whone AL, Caldwell MA, Billadeau DD, Rosen MK, Cullen PJ.
Curr Biol. 2014 July
Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane recycling.
McGough IJ, Steinberg F, Gallon M, Yatsu A, Ohbayashi N, Heesom KJ, Fukuda M, Cullen PJ. J Cell Sci. 2014 November