Diffusion of metabolites
and small non-nuclear molecules as well as active, mediated import
of protein and export of protein and RNA through the nuclear
envelope occurs through nuclear pore complexes or NPC’s.
NPC’s contain up to 100 different polypeptides which have
a combined mass of about 125 megadaltons. The channel available
for passive transport through the NPC is about 9-10 nm in diameter
while carrier mediated changes in the NPC result in a ~25 nm
channel used for larger, actively transported molecules. Of the
100 polypeptides, at least 8 of these are O-linked N-acetylglycosamine-modified
in mammalian cells. All of the mammalian O-linked glycoproteins
contain multiple copies of phenylalanine, glycine dipeptide repeats
dispersed throughout part of their sequence. Studies indicate
that the NPC O-linked glycoproteins have a direct role in nuclear
protein import. The accumulation of proteins in the nucleus is
mediated by short sequences of basic amino acids called nuclear
localization sequences (NLSs). These sequences are necessary
and sufficient to direct a protein or inert carrier to the nuclear
interior. Nuclear protein import is accomplished by two sequential,
energy dependent events. The first step, docking at the nuclear
pore complex, requires a 54/56 kDa nuclear localization signal
receptor (a-karyopherin, importin-a, SRP-a) and the nuclear transport
factor p97 (NTF97, b-karyopherin, importin-b). The second step,
translocation across the nuclear envelope (NE), requires the
GTP-binding protein, Ran/TC4.
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