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Cell BiologyCell Biology
S. Rahgozar,PhD
University of Isfahan
Faculty of Science
3. The nucleus
3.1. The nuclear envelope and nuclear traffic
1392-93
 Structure of the nuclear envelope
The space between the inner and outer nuclear membranes is directly
connected with the lumen of the endoplasmic reticulum.
 Nuclear membrane Compared to ER membrane is
 Similar in Function
having ribosomes bound to its surface)
 Different in composition (outer membrane contains proteins that bind to cytoskeleton
and
inner membrane carries specific proteins
(ie; those bound to nuclear lamina)
Nuclear membranes are permeable to small non polar molecules.
Small polar
molecules
Macromolecules
Ions
May pass
through
pores
 Nuclear lamina
Contains 60-80kd fibrous proteins called
lamins
Function: structural support of the nucleus
Model of lamin assembly
At least 7 distinct proteins of lamins are coded from 3 lamin genes of A, B and C
o Laminar modifications
Post translational addition of specific types of lipids (prenylation)
o Laminar interactions
 Histones H2A and H2B
 LBR (lamin B receptor) and Emerin
 Nuclear proteins that function in DNA synthesis, transcription or
chromatin
 Nuclear pore complex
 Diameter: 120 nm
 Molecular mass: 125,000 kd
 Composed of 30 proteins (nucleoporins) in
multiple copies
(~30×the size of a ribosome)Molecular traffic through nuclear
pore complexes
(20-40 kd)
Model of the nuclear pore complex
o A structure with 8fold symmetry organised around a large central channel
Nuclear localization signals (1984, Smith, Cell. studying SV40 T Ag)
 Selective transport of proteins
o Nuclear localization signals (specific aa sequences)
o Nuclear transport receptors (importins)
Involved in
replication
Involved in
chromatin
assembly
bipartite
Distribution of Ran/GTP across the nuclear envelope
Examples for Small GTP binding proteins: Ran, Rab, Rac, Rho, Cdc42, Arf,
Ran GAP: Ran
GTPase activating
protein
Ran GEF: Ran
guanine nucleotide
exchange factor
Protein import through the nuclear pore complex
NLS: nuclear localization
sequence
Transport
proceeds by
sequential
binding to
specific
nuclear pore
proteins
located
further and
further
toward the
nuclear side
of the pore
complex.
FG-
proteins
After release of importin Ran/GDP is transported back to the nucleus by NTF2 receptor
Nuclear export
NES: nuclear export
sequence
 exportins and importins are members of a
family named karyopherins
 Ran/GTP promotes the formation of stable
complexes between exportins and their cargo
proteins
Whereas
It dissociates the complexes between importins
and their cargos
3.nucleus.cell biology
 Regulation of nuclear protein import
 Inhibition by binding to a cytoplasmic inhibitory factor which masks its NLS
ubiquitin-mediated
Cell stimulation
 Inhibition by direct phosphorylation of NLS
 Transport of RNAs
Transport of a ribonucleoprotein complex (RNP) of 35-40kb from the nuclear pore in the salivary gland
of an insect (A), and unfolding of the RNA during its translocation to the cytoplasm
N
C
 Transport of tRNAs, rRNAs, miRNAs and snRNAs is through Ran/GTP
 Transport of mRNAs in through mRNA exporter (a complex of two proteins
including NTF2)
o tRNAs and miRNAs are exported by exportin-t and exportin5
Functional
snRNP
snRNP: small nuclear
ribonucleoprotein
5’7mGcap: 5’ 7-
methylguanosine cap
o Small RNAs function within the nucleus as components of the RNA processing
machinery.

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3.nucleus.cell biology

  • 1. Cell BiologyCell Biology S. Rahgozar,PhD University of Isfahan Faculty of Science 3. The nucleus 3.1. The nuclear envelope and nuclear traffic 1392-93
  • 2.  Structure of the nuclear envelope The space between the inner and outer nuclear membranes is directly connected with the lumen of the endoplasmic reticulum.
  • 3.  Nuclear membrane Compared to ER membrane is  Similar in Function having ribosomes bound to its surface)  Different in composition (outer membrane contains proteins that bind to cytoskeleton and inner membrane carries specific proteins (ie; those bound to nuclear lamina)
  • 4. Nuclear membranes are permeable to small non polar molecules. Small polar molecules Macromolecules Ions May pass through pores  Nuclear lamina Contains 60-80kd fibrous proteins called lamins Function: structural support of the nucleus
  • 5. Model of lamin assembly At least 7 distinct proteins of lamins are coded from 3 lamin genes of A, B and C
  • 6. o Laminar modifications Post translational addition of specific types of lipids (prenylation)
  • 7. o Laminar interactions  Histones H2A and H2B
  • 8.  LBR (lamin B receptor) and Emerin  Nuclear proteins that function in DNA synthesis, transcription or chromatin
  • 9.  Nuclear pore complex  Diameter: 120 nm  Molecular mass: 125,000 kd  Composed of 30 proteins (nucleoporins) in multiple copies (~30×the size of a ribosome)Molecular traffic through nuclear pore complexes (20-40 kd)
  • 10. Model of the nuclear pore complex o A structure with 8fold symmetry organised around a large central channel
  • 11. Nuclear localization signals (1984, Smith, Cell. studying SV40 T Ag)  Selective transport of proteins o Nuclear localization signals (specific aa sequences) o Nuclear transport receptors (importins) Involved in replication Involved in chromatin assembly bipartite
  • 12. Distribution of Ran/GTP across the nuclear envelope Examples for Small GTP binding proteins: Ran, Rab, Rac, Rho, Cdc42, Arf, Ran GAP: Ran GTPase activating protein Ran GEF: Ran guanine nucleotide exchange factor
  • 13. Protein import through the nuclear pore complex NLS: nuclear localization sequence Transport proceeds by sequential binding to specific nuclear pore proteins located further and further toward the nuclear side of the pore complex. FG- proteins After release of importin Ran/GDP is transported back to the nucleus by NTF2 receptor
  • 14. Nuclear export NES: nuclear export sequence  exportins and importins are members of a family named karyopherins  Ran/GTP promotes the formation of stable complexes between exportins and their cargo proteins Whereas It dissociates the complexes between importins and their cargos
  • 16.  Regulation of nuclear protein import  Inhibition by binding to a cytoplasmic inhibitory factor which masks its NLS ubiquitin-mediated Cell stimulation  Inhibition by direct phosphorylation of NLS
  • 17.  Transport of RNAs Transport of a ribonucleoprotein complex (RNP) of 35-40kb from the nuclear pore in the salivary gland of an insect (A), and unfolding of the RNA during its translocation to the cytoplasm N C  Transport of tRNAs, rRNAs, miRNAs and snRNAs is through Ran/GTP  Transport of mRNAs in through mRNA exporter (a complex of two proteins including NTF2)
  • 18. o tRNAs and miRNAs are exported by exportin-t and exportin5 Functional snRNP snRNP: small nuclear ribonucleoprotein 5’7mGcap: 5’ 7- methylguanosine cap o Small RNAs function within the nucleus as components of the RNA processing machinery.