Head


Christoph Kaether
Christoph Kaether

Postdocs

Matthias Faßler

Xiaolin Li

Malle Soom

Christina Valkova

PhD Students

Iree Chang

Andreas Krämer

N. N. ( » Job offer)

Master Students

Sebastian Klare

Technicians

Daniela Reichenbach



Kaether Laboratory

Membrane trafficking

 

Currently in the lab three major projects are pursued:

Alzheimer Disease

Alzheimers Disease is characterised by the deposition of amyloid plaques in the brain. Plaques are composed of Abeta, a 40-42 amino acid long peptide. Two proteases, beta- and gamma-secretase, cleave a larger precursor, the APP, to release Abeta. Although a wealth of information about Abeta generation is available, there are many open questions: Where do the secretases meet their substrate? How is this interaction regulated? Do the secretases have roles other than cleaving APP, i.e. regulating transport of APP and other proteins? Are there differences between neurons and undifferentiated cells? We also want to understand in detail how gamma-secretase is assembled and transported to its site of action in the cell and what the role of dysfunctions in axonal transport plays in AD.

 

The video shows a field of axons

 

 

 

» The video shows a field of axons from cultured hippocampal neurons transfected with APP-YFP and imaged by time-lapse videomicroscopy. Frames were taken at 1 sec intervals. Taken from Kaether et. al. (2000) Mol Biol Cell. 11, 1213-1224, with permission.

 

 

 

 

Rer1, a novel retrieval receptor

We recently identified a mammalian retrieval receptor, Rer1. In analogy to the KDEL receptor Rer1 transports escaped proteins back from the cis-Golgi to the ER. Whats special about Rer1 is that it recognizes sorting signals in transmembrane domains. We want to study the molecular details of transmembrane domain mediated sorting and the role of Rer1 therein.

 

Neuronal Notch

The Notch receptor is essential for development, but also involved in learning and memory. We study where and how in neurons Notch is processed and how the signal transduction is mediated.

 

Methods

We use a large number of different methods. Among those are cloning of reporter proteins or GFP-tagged proteins and site-directed mutagenesis of these. Expression constructs are transfected in cell lines or primary neurons and analysed by microscopy (video-, confocal-, apotome-) or biochemically (blot, IP, deglycosylation and others). In addition we use mouse models.

 

The Research Group
top row: Li, Kaether, Krämer, Soom, Klare.
bottom row: Chen, Chang, Hünniger, Reichenbach, Valkova.
missing: Fassler.

 

Recent selected publications

  • Fassler M, Zocher M, Klare S, Guzman de la Fuente A, Scheuermann J, Capell A, Haass C, Valkova C, Veerappan A, Schneider D, Kaether C (2009) Masking of transmembrane-based retention signals controls ER-export of gamma-secretase. Traffic [Epub]
  • Kurth I, Pamminger T, Hennings JC, Soehendra D, Huebner AK, Rotthier A, Baets J, Senderek J, Topaloglu H, Farrell SA, Nürnberg G, Nürnberg P, De Jonghe P, Gal A, Kaether C, Timmerman V, Hübner CA (2009) Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nature Genetics, 41, 1179-81 [PubMed]
  • Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro-O M, Kaether C (2009) Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Letters, 583, 3221-4. [PubMed]
  • Kaether C, Scheuermann J, Fassler M, Zilow S, Shirotani K, Valkova C, Novak B, Kacmar S, Steiner H, Haass C (2007) Endoplasmic reticulum retention of the gamma-secretase complex component Pen2 by Rer1. EMBO Rep. 8, 743-748. [PubMed]
  • Kaether C, Schmitt S, Willem M, Haass C (2006) Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface. Traffic. 7, 408-415. [PubMed]
  • Kaether C, Capell A, Edbauer D, Winkler E, Novak B, Steiner H, Haass C (2004) The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity. EMBO J. 23, 4738-4748. [PubMed]
  • Kaether C, Lammich S, Edbauer D, Ertl M, Rietdorf J, Capell A, Steiner H, Haass C (2002) Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane. J Cell Biol. 158, 551-561. [PubMed]
  • Kaether C, Skehel P, Dotti CG (2000) Axonal membrane proteins are transported in distinct carriers: a two-color video microscopy study in cultured hippocampal neurons. Mol Biol Cell. 11, 1213-1224. [PubMed]

 

Interested, highly motivated people on all levels are always encouraged to apply or send an informal request to ckaether at fli-leibniz.de.

 

We gratefully acknowledge funding by DFG, SFB604 and the Hans-und-Ilse Breuer Stiftung.

Last update: July 3, 2008
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