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SUMMARY:Nuclear Trafficking and Maxwell's Daemon - Dr. Murray Stewart\, LM
 B
DTSTART:20140302T103000Z
DTEND:20140302T112000Z
UID:TALK51194@talks.cam.ac.uk
CONTACT:Trinity College Science Society
DESCRIPTION:Eukaryotic cells are characterized by having a nucleus\, in wh
 ich the genetic material is stored\, surrounded by a cytoplasm where prote
 ins are synthesized.  This arrangement poses a question of communication. 
  The information stored in DNA in chromosomes in the nucleus is first tran
 scribed into messenger RNA (mRNA) that is then transported out of the nucl
 eus\, through nuclear pores\, to the cytoplasm where it is translated into
  proteins.  Many of these proteins ultimately function in the nucleus and 
 so have to be imported from the cytoplasm.  The nucleus is separated from 
 the cytoplasm by the nuclear membrane and transport between the two compar
 tments is mediated by nuclear pores.  The transport of large macromolecule
 s\, such as proteins and RNAs\, though the nuclear pores is selective and 
 requires metabolic energy.  The nuclear pores themselves have a ~30 nm dia
 meter central transport channel\, but movement through this channel is res
 tricted by its containing a high concentration of proteins (called “nucl
 eoporins”) in which the chains lack regular structure.  The high concent
 ration of these unfolded protein chains restricts the conformations they c
 an adopt and thus reduces their entropy\, in a manner analogous to the way
  de Gennes proposed for the formation of polymer brushes.  Inserting macro
 molecules into this gel of nucleoporins is inhibited because it increases 
 the molecular crowding\, further reducing their entropy.  Specific transpo
 rt molecules are used to overcome this inhibition by interacting with the 
 nucleoporins in a way that releases sufficient free energy to overcome the
  loss of entropy.  These transport factors do not\, however\, establish di
 rectionality of transport and simply diffuse back and forth through the po
 res with their bound cargo.  Directionality is instead imposed by regulati
 ng the formation of the cargo:carrier complex in one compartment and its d
 isassembly in the other compartment.  Thus\, energy is expended in sorting
  the material rather than actually transporting it through the pores\, whi
 ch happens simply by diffusion.  Nuclear trafficking can therefore be thou
 ght of as a form of thermal ratchet in which Brownian motion is rectified.
   In nuclear protein import\, for example\, the energy is supplied by the 
 hydroplysis of GTP.  Thus\, carriers of the karyophen family of transport 
 factors bind their cargoes in the cytoplasm and diffuse back and forth thr
 ough the pores.  In the nucleus\, the cargo:carrier complex is dissociated
  by the GTPase Ran in its GTP-bound form.  The karyophenin:RanGTP complex 
 then diffuses back to the cytoplasm where the GTP is hydrolyzed\, leading 
 to the dissociation of Ran and freeing the carrier for another transport c
 ycle.  The Ran is also imported back to the nucleus\, where it is recharge
 d with GTP.
LOCATION:Winstanley Lecture Theatre
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