Intracellular Compartments and
Protein Transport (BOOK)
Chapter 12 pp 641-681, 683-684
Intracellular compartments and protein sorting
The compartmentalisation of cells
Intracellular membrane systems form enclosed compartments that are separate from the cytosol.
The major intracellular compartments of an animal cell are:
- Nucleus contains the genome
- Cytoplasm consists of cytoplasm and organelles
- Cytosol is the cytoplasm without organelles and
performs most intermediary metabolism
- Endoplasmic reticulum (ER) – two variants rough
(with ribosomes) and smooth (without
ribosomes) and the ER functions as storage for
Ca+
- Golgi apparatus consists of organised stacks of
disc like compartments called Golgi cisternae.
- Mitochondria generate most ATP
- Chloroplasts are specialised plastids and
generate most of ATP in plants
- Lysosomes contain digestive enzymes
- Endosomes
- Peroxisomes are small vesicular compartments
that contain enzymes
Evolutionary origins
The precursors of the first eukaryotic cells are thought to have
been relatively simple cells hat, like most bacterial and archaeal
cells have a plasma membrane but no internal membranes.
Intracellular compartments in eukaryotes can be described in
four different families:
1. Nucleus and cytosol – communicate through nuclear
pore complexes
2. ER, Golgi apparatus, endosomes, lysosomes, transport
vesicles and peroxisomes – functions in secretion and
endocytoses
3. Mitochondria
4. Plastids (in plants)
Protein movement
The amino acid sequence of proteins can contain sorting signals that direct their delivery to locations
outside the cytosol or to organelle surfaces. Some proteins do not have these sorting signals and
remain in the cytosol as permanent residents.
Each mode of protein transfer is guided by sorting signals in the transported protein which are
recognised by complementary sorting receptors.
, There are three different ways by which proteins move from one compartment to another:
1. In gated transport move between the nucleus and cytosol through nuclear pore complexes.
2. In protein translocation, transmembrane protein translocators transport specific proteins
across a membrane from the cytosol into another space.
3. In vesicular transport membrane-enclosed transport intermediates ferry proteins from one
topologically equivalent compartment to another.
Signal sequences are often found in the N-terminus (start of a protein referring to the free amine
group) and in many cases specialised signal peptidases remove this sequence once sorting process is
completed.
Signal patches are sorting signal composed of multiple internal amino acid sequences that form to an
3D structure.
Each signal sequence specifies a particular destination in the cell. These are recognised by
complementary sorting receptors that guide proteins to their appropriate destination where the
receptors unload their cargo.
Constructing new cells
During cell division, the cell organelles needs to be duplicated as well. This is done by incorporating
new molecules into the existing organelles, thereby enlarging them, the enlarged organelles then
divide and are distributed to the daughter cells.
The transport of molecules between the nucleus and cytosol
The nuclear envelope consists of two membranes and encloses the DNA and defines the nuclear
compartment. The inner nuclear membrane contains proteins that act as binding sites for
chromosomes and for the nuclear lamina (provides structural support). The inner nuclear membrane
is surrounded by the outer nuclear membrane which is studded with ribosomes and is continues
with the membrane of the ER.
Nuclear pore complexes
Nuclear pore complexes (NPCs) perforate the nuclear envelope in all eukaryotes and each NPC is
composed of about 30 nucleoporins (proteins).
Small molecules (<5000 dalton) diffuse fast, large proteins (>5000 dalton) diffuse slower and proteins
larger than 6000 dalton cannot enter by passive diffusion.
Sorting signals called nuclear localisation signals (NLSs) are responsible for the selectivity of the
active nuclear import process. NLSs can be located everywhere in the sequence and are thought to
form loops or patches at the protein surface.
Nuclear import receptors are necessary for nuclear import because they can bind (indirectly and
directly) to nuclear proteins.
Nuclear export works like nuclear import but in reverse. This transport system relies on nuclear
export signals on the macromolecules to be exported as well as on complementary nuclear export
receptors. These receptors bind to both the export signal and the NPC protein.
Ran GTPase
The GTPase Ran stores energy which is required for both nuclear import and export. Ran is a
molecular switch that can exists in two conformational states, depending on whether GDP or GTP is
bound. A cytosolic GTPase activating protein (GAP) trigger GTP hydrolysis and thus converts Ran-GTP
to Ran-GDP and the guanine exchange factor (GEF) is responsible for the reverse process. The Ran-
GAP is located in the cytosol and Ran-GEF in the nucleos so the cytosol mainly contains Ran-GDP and
the nucleus Ran-GTP.
Protein Transport (BOOK)
Chapter 12 pp 641-681, 683-684
Intracellular compartments and protein sorting
The compartmentalisation of cells
Intracellular membrane systems form enclosed compartments that are separate from the cytosol.
The major intracellular compartments of an animal cell are:
- Nucleus contains the genome
- Cytoplasm consists of cytoplasm and organelles
- Cytosol is the cytoplasm without organelles and
performs most intermediary metabolism
- Endoplasmic reticulum (ER) – two variants rough
(with ribosomes) and smooth (without
ribosomes) and the ER functions as storage for
Ca+
- Golgi apparatus consists of organised stacks of
disc like compartments called Golgi cisternae.
- Mitochondria generate most ATP
- Chloroplasts are specialised plastids and
generate most of ATP in plants
- Lysosomes contain digestive enzymes
- Endosomes
- Peroxisomes are small vesicular compartments
that contain enzymes
Evolutionary origins
The precursors of the first eukaryotic cells are thought to have
been relatively simple cells hat, like most bacterial and archaeal
cells have a plasma membrane but no internal membranes.
Intracellular compartments in eukaryotes can be described in
four different families:
1. Nucleus and cytosol – communicate through nuclear
pore complexes
2. ER, Golgi apparatus, endosomes, lysosomes, transport
vesicles and peroxisomes – functions in secretion and
endocytoses
3. Mitochondria
4. Plastids (in plants)
Protein movement
The amino acid sequence of proteins can contain sorting signals that direct their delivery to locations
outside the cytosol or to organelle surfaces. Some proteins do not have these sorting signals and
remain in the cytosol as permanent residents.
Each mode of protein transfer is guided by sorting signals in the transported protein which are
recognised by complementary sorting receptors.
, There are three different ways by which proteins move from one compartment to another:
1. In gated transport move between the nucleus and cytosol through nuclear pore complexes.
2. In protein translocation, transmembrane protein translocators transport specific proteins
across a membrane from the cytosol into another space.
3. In vesicular transport membrane-enclosed transport intermediates ferry proteins from one
topologically equivalent compartment to another.
Signal sequences are often found in the N-terminus (start of a protein referring to the free amine
group) and in many cases specialised signal peptidases remove this sequence once sorting process is
completed.
Signal patches are sorting signal composed of multiple internal amino acid sequences that form to an
3D structure.
Each signal sequence specifies a particular destination in the cell. These are recognised by
complementary sorting receptors that guide proteins to their appropriate destination where the
receptors unload their cargo.
Constructing new cells
During cell division, the cell organelles needs to be duplicated as well. This is done by incorporating
new molecules into the existing organelles, thereby enlarging them, the enlarged organelles then
divide and are distributed to the daughter cells.
The transport of molecules between the nucleus and cytosol
The nuclear envelope consists of two membranes and encloses the DNA and defines the nuclear
compartment. The inner nuclear membrane contains proteins that act as binding sites for
chromosomes and for the nuclear lamina (provides structural support). The inner nuclear membrane
is surrounded by the outer nuclear membrane which is studded with ribosomes and is continues
with the membrane of the ER.
Nuclear pore complexes
Nuclear pore complexes (NPCs) perforate the nuclear envelope in all eukaryotes and each NPC is
composed of about 30 nucleoporins (proteins).
Small molecules (<5000 dalton) diffuse fast, large proteins (>5000 dalton) diffuse slower and proteins
larger than 6000 dalton cannot enter by passive diffusion.
Sorting signals called nuclear localisation signals (NLSs) are responsible for the selectivity of the
active nuclear import process. NLSs can be located everywhere in the sequence and are thought to
form loops or patches at the protein surface.
Nuclear import receptors are necessary for nuclear import because they can bind (indirectly and
directly) to nuclear proteins.
Nuclear export works like nuclear import but in reverse. This transport system relies on nuclear
export signals on the macromolecules to be exported as well as on complementary nuclear export
receptors. These receptors bind to both the export signal and the NPC protein.
Ran GTPase
The GTPase Ran stores energy which is required for both nuclear import and export. Ran is a
molecular switch that can exists in two conformational states, depending on whether GDP or GTP is
bound. A cytosolic GTPase activating protein (GAP) trigger GTP hydrolysis and thus converts Ran-GTP
to Ran-GDP and the guanine exchange factor (GEF) is responsible for the reverse process. The Ran-
GAP is located in the cytosol and Ran-GEF in the nucleos so the cytosol mainly contains Ran-GDP and
the nucleus Ran-GTP.
