1 Molecular Biology Medicine Part II a Ettore Sansavini Health Science Foundation – ONLUS Lugo (Ravenna), Italy SWITH Carlo Ventura Professor of Molecular Biology University of Bologna, Italy

Nuclear Architecture/Overview Double-membrane envelope Has lumen that is continuous with ER Outer membrane also has ribosomes like ER Nuclear envelope has pores –large, complex structures with octahedral geometry –allow proteins and RNAs to pass –transport of large proteins and RNAs requires energy Many nuclear proteins have nuclear localization signals (NLS) –short basic peptides, not always at N-terminus

Nuclear architecture (cont.) nuclear skeleton (lamina) –intermediate filaments (lamins) –anchor DNA and proteins (i.e., chromatin) to envelope Nucleolus –site of pre-rRNA synthesis and ribosome assembly

Nucleus with large nucleolus. Stars indicate heterogeneity in the nucleolus.

d – partially assembled ribosomes passing through pores (side view) Freeze fracture EM view  c –pores face on view thru tunnel

Model of nuclear pore (A is top view) Buchanan et al.

Kinase Transcription Factor     Cytosolic phosphorylation of Kinases or TF exposes NLS (red) that are recognized by cariopherins ( ,  ) The entire complex is recognized by the active form (GTP bound) of a mobile receptor (Ran-TC)   Ran

Nuclear Signaling

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