Protein topogenesis

Protein transport into the endoplasmic reticulum

The first step in the topogenesis of secretory and plasma membrane proteins or of proteins destined to compartments of the secretory pathway is in most cases the translocation into the endoplasmec retiiculum. Currently we are investigating the following aspects of this process:.

 

Ribosome binding and dynamics at the translocation site

Prinz, A., Behrens, C., Rapoport, T.A., Hartmann, E. and Kalies, K.-U. (2000) Evolutionarily conserved binding of ribosomes to the translocation channel via the large ribosomal RNA. EMBO J. 19, 1900-1906. 
Prinz, A., Hartmann, E. and Kalies, K.-U. (2000) Sec61p is the main ribosome receptor in the endoplasmic reticulum of Saccharomyces cerevisiae. Biol. Chem., 381, 1025-1029. 

 

Interaction of the translocation site with components involved in ER associatied protein degradation

Kalies, K.-U., Allan, S., Sergeyenko, T., Kröger, H., Römisch, K. (2005) The protein translocation channel binds proteasomes to the endoplasmic  reticulum membrane  EMBO J. 24, 2284-2293.

 

Evolutionary conservation of the translocation machinery and linked ER components

Lenk, U., Yu, H., Walter, J., Gelman, M.S., Hartmann, E., Kopito, R.R., Sommer, T. (2002) A role for mammalian Ubc6 homologues in ER-associated protein degradation. J Cell Sci. 115, 3007-3014. 
Dilks, K., Rose, W., Hartmann, E., and Pohlschröder, M. (2003) Prokaryotic Utilization of the Twin-Arginine Translocation Pathway: Genomic Survey. J. Bact. 185, 1478-1483. 
Hartmann, E. (2003) Ähnlichkeiten der Primärstruktur des Sec61ß mit anderen Transportfaktoren der Prokaryonten und ihre Bedeutung für ein Modell der Evolution des Translokons. FOCUS MUL 20, 103-107. 
Dilcher M, Veith B, Chidambaram S, Hartmann E, Schmitt HD, Fischer von Mollard G. (2003) Use1p is a yeast SNARE protein required for retrograde traffic to the ER. EMBO J. 22, 3664-3374.
Pohlschröder, M., Hartmann, E., Hand, N.J., Dilks, K., Haddad, A. (2005) Diversity and Evolution of Protein Translocation Annual Review of Microbiology 59, 91-111.

Trautwein, M., Schindler, C., Gauss, R., Dengjel, J., Hartmann, E., Spang, A. (2006) Arf1p, Chs5p and the ChAPs are required for export of specialized cargo from the Golgi EMBO J. 25, 943-954.

 

Functional and structural analysis of components of the translocation site

Van den Berg, B., Clemons, W.R. Jr., Collinson, I., Modis, Y., Hartmann, E., Harrison, S.C., Rapoport, T.A. (2004) X-ray structure of a protein-conducting channel Nature 427, 36-44.

Hori, O., Miyazaki, M., Tamatani, T., Ozawa, K., Takano, K., Okabe, M., Ikawa, M., Hartmann, E., Mai, P., Stern, D.M., Kitao, Y., Ogawa, S. (2006) Deletion of SERP1/RAMP4, a component of the endoplasmic reticulum (ER) translocation sites, leads to ER stress Molecular and Cellular Biology 26, 4257-4267.

 

Transport between nucleoplasm and cytoplasm

Functional analysis of mammalian importin alpha

Mammlian cells have seven different genes coding for importin alpha, a component of the so-called "classical" protein import pathway into the nucleus. Currently we are investigating the specific cellular funtions of the different importin proteins:

Quensel C, Friedrich B, Sommer T, Hartmann E, Köhler M (2004) In vivo analysis of importin alpha proteins reveals cellular proliferation and substrate specifity Molecular and Cellular Biology 24, 10246-10255.

Friedrich B, Quensel C, Sommer T, Hartmann E, Köhler M (2006) Nuclear localization signal and protein context both mediate importin alpha specifity of nuclear import substrates Molecular and Cellular Biology 26, 8697-8709.