RESEARCH - Daniel Kümmel
and Structural biology
Coordination of intracellular trafficking and fusion by RabGEF
Extracellular substances and cell surface proteins are internalized by endocytic vesicles, which fuse to form early endosome. These organelles are positive for the marker GTPase Rab5 and here cargo is sorted and recycled. Alternatively, the content is delivered to the lysosome for degradation, which requires the maturation into a late endosome through the conversion into a Rab7-positive membrane. The molecular mechanism of this process is poorly understood, but the Mon1-Ccz1 (MC1) complex has been identified as a key player: MC1 is recruited by Rab5 and acts as GEF (activator) for Rab7 and thus initiates organelle conversion. We study the structure and function of MC1 to gain better insight into the mechanism and regulation of endosomal maturation.
Klink B.U., Herrmann E., Antoni C., Langemeyer L., Kiontke S., Gatsogiannis C., Ungermann C., Raunser S., Kümmel D. (2022)
Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation.
Proc Natl Acad Sci USA, 119, doi: 10.1073/pnas.2121494119
Langemeyer et al. (2020)
A conserved and regulated mechanism drives endosomal Rab transition.
eLife doi: 10.7554/eLife.56090
Kiontke et al. (2017)
Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1.
Nat Commun doi: 10.1038/ncomms14034