Molecular and Functional Analysis of Oligodendroglial Exosomes

Christina Müller

 

We perform proteomic and transcriptomic profiling of small extracellular vesicles and exosomes isolated from primary oligodendrocytes (OL-sEVs) to characterize their molecular content. Using different isolation procedures, we aim at deciphering different OL-sEV subtypes and correlating functions. Our previous work indicates that OL-sEVs promote the neuronal metabolic activity and axonal transport. We use transgenic mouse models, which exhibit secondary axonal degeneration (e.g. PLP-ko and CNP-ko mice) and study mutant-derived OL-sEVs, lacking the functional competence of wild-type OL-sEVs, to decipher the molecular cargo and signalling pathways relevant for neuronal support and axonal maintenance.

 

 

Relevant Publications

Oligodendrocytes support axonal transport and maintenance via exosome secretion. Frühbeis C, Kuo-Elsner WP, Müller C, Barth K, Peris L, Tenzer S, Möbius W, Werner HB, Nave KA, Fröhlich D, Krämer-Albers EM. PLoS Biol. 2020 Dec 22;18(12):e3000621. doi: 10.1371/journal.pbio.3000621. Epub ahead of print. PMID: 33351792.

Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain. Mukherjee C, Kling T, Russo B, Miebach K, Kess E, Schifferer M, Pedro LD, Weikert U, Fard MK, Kannaiyan N, Rossner M, Aicher ML, Goebbels S, Nave KA, Krämer-Albers EM, Schneider A, Simons M. Cell Metab. 2020 Jun 5:S1550-4131(20)30300-4. doi: 10.1016/j.cmet.2020.05.019. Online ahead of print. PMID: 32531201

Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation. Fröhlich D, Kuo WP, Frühbeis C, Sun JJ, Zehendner CM, Luhmann HJ, Pinto S, Toedling J, Trotter J, Krämer-Albers EM. Philos Trans R Soc Lond B Biol Sci. 2014 Sep 26;369(1652):20130510. doi: 10.1098/rstb.2013.0510. PMID: 25135971 Free PMC article.

Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. Frühbeis C, Fröhlich D, Kuo WP, Amphornrat J, Thilemann S, Saab AS, Kirchhoff F, Möbius W, Goebbels S, Nave KA, Schneider A, Simons M, Klugmann M, Trotter J, Krämer-Albers EM. PLoS Biol. 2013 Jul;11(7):e1001604. doi: 10.1371/journal.pbio.1001604. Epub 2013 Jul 9. PMID: 23874151 Free PMC article.

Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Krämer-Albers EM, Bretz N, Tenzer S, Winterstein C, Möbius W, Berger H, Nave KA, Schild H, Trotter J. Proteomics Clin Appl. 2007 Nov;1(11):1446-61. doi: 10.1002/prca.200700522. Epub 2007 Oct 16. PMID: 21136642

 

Funding


DFG KR3668/1-1 and KR3668/1-2

 

Collaborators

Klaus-Armin Nave

Wiebke Möbius

Hauke Werner (Göttingen)

Sandra Göbbels (Göttingen)

Mikael Simons

Leticia Peris

Stefan Tenzer

 

Former Lab Members

Jesa Amphornrat

Martin Auber

Kerstin Barth

Niko Bretz

Dominik Fröhlich

Carsten Frühbeis

Marla Herr

Wen Ping Kuo-Elsner

Sebastian Thilemann

Monika Tießen