WEEK 6 (Cytoplasm membrane systems) Flashcards
What are the main functions of the Cytosol?
- connects all of the intracellular compartments
- contains many metabolic pathways
- protein synthesis
- cytoskeleton
What is the theory of the origin of mitochondria?
Mitochondria are thought to have originated when an aerobic prokaryote was engulfed by a larger pre-eukaryotic cell
What is the main function of internal membranes?
- create enclosed compartments and organelles
- segregate metabolic processes
What happens during ‘Protein sorting’ and what does it depend on?
Protein sorting is a transfer process where a unique set of proteins are transferred selectively from the cytosol where they are made to the compartment where they are used
It depends on signals built into the amino acid sequence of the proteins that directs the protein to the organelle in which it is required
What are some examples of the function of the Smooth ER in cells?
- site of steroid hormone synthesis in some endocrine cells of the adrenal gland
- site where a variety of organic molecules (including alcohol) are detoxified in liver cells
What are the main functions and properties of the nucleus?
- contains main genome
- DNA and RNA synthesis
- surrounded by a double membrane (NUCLEAR ENVELOPE)
- communicates with the cytosol via NUCLEAR PORES
- continuous with the membrane of the endoplasmic reticulum
What are the main functions and properties of the endoplasmic reticulum?
- synthesis of most lipids
- synthesis of proteins for distribution to many organelles and to the plasma membrane
- major site of synthesis of new membranes in the cell
- RER contains ribosomes attached to cytosolic surface
What is the main function of the Golgi apparatus?
modification, sorting and packaging of proteins and lipids either for secretion or delivery to another organelle
What is the main function of Lysosomes?
Intracellular degradation
What is the main function of Endosomes?
Sorting of endocytosed material
What is the main function of Mitochondria?
ATP synthesis by oxidative phosphorylation
What is the main function of Chloroplasts?
ATP synthesis and carbon fixation by photosynthesis
What is the main function of Peroxisomes?
Oxidation of toxic molecules
What is the theory of the origin of the nucleus and endoplasmic reticulum?
The plasma membrane of an ancient prokaryotic cell with its attached DNA could have invaginated and formed a two-layered envelope of membrane completely surrounding the DNA. This envelope eventually pinched off completely and other portions of the invaginated membrane formed the ER.
What is protein targeting/protein sorting?
The mechanism by which a cell transports proteins to the appropriate positions in the cell or outside of it
Which organelles have proteins delivered directly from the cytosol?
- mitochondria
- peroxisomes
- interior of the nucleus
Which organelles have proteins and lipids delivered indirectly via the endoplasmic reticulum?
- Golgi apparatus
- Lysosomes
- Endosomes
- Inner nuclear membrane
What are the three mechanisms that proteins are transported into organelles?
- transport through nuclear pores (nucleus)
- protein translocators (ER, mitochondria, chloroplasts, peroxisomes)
- vesicular transport (Golgi, lysosomes, cell surface)
What happens if localisation/sorting signals are removed?
the protein does not arrive at the required destination
Describe the structure of the nucleus
- NUCLEAR ENVELOPE - defines the nuclear compartment & formed from two membranes
- INNER NUCLEAR MEMBRANE - contains proteins that act as binding sites for the chromosomes and provide anchorage for the nuclear lamina
- NUCLEAR LAMINA - protein filaments that provide structural support for the nuclear envelope
- OUTER NUCLEAR MEMBRANE - membrane similar composition as the ER membrane (since it is continuous with ER)
- NUCLEAR PORES - form the gates which all molecules enter or leave the nucleus
What is distinguishable about the nuclear pore?
It is a large, elaborate structure composed of a complex of about 30 different proteins
What is the name of the signal sequence that directs a protein from the cytosol into the nucleus?
Nuclear localisation signal
What is distinguishable about nuclear localisation signals?
consists of one or two short sequences containing several positively charged lysines or arginines
What do many of the proteins that line the nuclear pore contain?
extensive, unstructured regions in which the polypeptide chains are largely disordered
What is the nuclear localisation signal on proteins destined for the nucleus recognised by?
Cytosolic proteins called nuclear import receptors
What is the function of Nuclear import receptors?
Nuclear import receptors recognise the nuclear localisation signal on the designated proteins and interact with the cytosolic fibrils that extend from the side of the pore. After cargo delivery, the receptors return to the cytosol via nuclear pores for reuse.
(similar types of transport receptors, operating in the reverse direction, export MRNAs from the nucleus)
Describe the stages of a nuclear protein entering the nucleus
1) Nuclear import receptor picks up a prospective nuclear protein in the cytosol and enters the nucleus where it encounters a small GTPase called Ran which carries a molecule of GTP
2) Ran-GTP binds to the import receptor causing it to release the nuclear protein; when cargo is released, the receptor (still carrying Ran-GTP) is transported back through the pore to the cytosol
3) An accessory protein triggers Ran to hydrolyse its bound GDP. Ran-GDP falls off the import receptor which is then free to bind to another protein destined for the nucleus.
[a similar cycle operates to export mRNAs and ribosomal subunits from the nucleus into the cytosol, using nuclear export receptors that recognise nuclear export signals]
What is distinguishable about mitochondrial precursor proteins when they enter the mitochondria?
The mitochondrial precursor proteins are unfolded during import into the mitochondria
Describe the stages of mitochondrial precursor proteins entering the mitochondria
1) A mitochondrion has an outer and inner membrane which must be crossed for a mitochondrial precursor protein to enter the organelle
2) Mitochondrial signal sequence on a mitochondrial precursor protein is recognised by a receptor in the outer mitochondrial membrane which is associated with a protein translocator.
3) Complex of receptor, precursor protein and translator diffuses laterally in the outer membrane until it encounters a second translocator in the inner membrane. The two translocators transport the protein across both the outer and inner membranes, unfolding the protein in the process.
4) Chaperone proteins inside the organelles help to pull the protein across the two membranes and to fold it once it is inside.
What is the name of the proteins that transport phospholipids to organelles and what is its other function?
Lipid-carrying proteins
Extract a phospholipid molecule from one membrane and deliver it into another
What is the anatomy of the Peroxisome?
- plasma membrane containing a lipid bilayer
- urate oxidase crystalline core
- similar to lysosomes but contains oxidases (enzymes that produce H2O2) rather than hydrolases
What are the functions of peroxisomes?
- destroy certain products formed from oxygen (especially hydrogen peroxide that can be toxic to cells)
- breakdown toxins, alcohol and fatty acids
- peroxisomes of the liver cells detoxify the alcohol a person drinks
What is known about the transport mechanism of peroxisomes?
still mysterious but imported proteins do not need to unfold to enter the peroxisome
Where do peroxisomal proteins originate from?
- the cytosol
- via vesicles from the ER membrane (these vesicles either fuse with preexisting peroxisomes or import peroxisomal proteins from the cytosol to grow into mature peroxisomes
What are some examples of Peroxisome biogenesis disorders that are caused by defective peroxisomes?
- Zellweger Syndrome (ZS) (most severe)
- Neonatal Adrenoleukodystrophy (NALD)
- Infantile Refuse Disease (IRD) (least severe)
What is Zellweger syndrome?
Zellweger syndrome is caused by mutations in any one of at least 12 genes but mutations in the PEX1 gene are the most common cause. It is an autosomal recessive disorder in which there is no cure; treatment is generally symptomatic and supportive. Signs and symptoms usually appear during the newborn period.
SYMPTOMS:
- poor muscle tone (hypotonia)
- poor feeding
- seizures
- hearing loss
- vision loss
- distinctive facial features
- skeletal abnormalities
What is the importance of the PEX1 gene?
The PEX1 gene provides instructions for making a protein called PEROXISOMAL BIOGENESIS FACTOR 1 (Pex1p) which is a peroxin.
Peroxins are essential for the formation and normal functioning of cell structures called Peroxisomes.
What are the other names for Neonatal Adrenoleukodystrophy?
- NALD
- Adrenoleukodystrophy autosomal neonatal form
What are Leukodystrophies?
A group of rare, progressive, metabolic, genetic diseases that affect the brain, spinal cord and often the peripheral nerves
What is Neonatal Adrenoleukodystrophy?
NALD is a variant of intermediate severity of the PBD-Zellweger syndrome spectrum characterised by Hypotonia, Leukodystrophy and vision and sensorineural hearing deficiencies.
PBD-ZSS is caused by mutations in one of 13 PEX genes encoding peroxins which lead to abnormal peroxisome disorders.
Diagnosis: NALD is suspected on physical examination and confirmed with biochemical evaluation.
Prognosis: most patients die in infancy and early childhood but some have lived until their teenage years
How many mutations in the PEX1 gene have been identified in people with Zellweger spectrum disorder?
114
What are some symptoms of Neonatal Adrenoleukodystrophy?
- Abnormality of the palate
- Abnormal metabolism/homeostasis
- Abnormal liver
- Anterverted nares
- loss of developmental milestones
- long, narrow head
- increased reflexes
- low or weak muscle tone
- involuntary, rapid, rhythmic eye movements
- short stature
- cross-eyed
- broad nasal bridge
What are Peroxisome Biogenesis Disorders Zellweger Syndrome Spectrum (PBD-ZSS)?
A group of inherited genetic disorders that damage the white matter of the brain and affect motor movements
What is Infantile Refsum Disease?
IRD is the mildest of a group of disorders called PBD-ZSS (Peroxisome biogenesis disorders Zellweger syndrome spectrum). It is caused by mutations in one of the PEX genes encoding peroxisomal biogenesis factor 1 which is part of a group of proteins called Peroxins; it’s inherited in an autosomal recessive manner.
Life expectancy, medical complications and the degree of neurological impairment can vary. Survival into adulthood is possible.
SYMPTOMS:
- Limited peripheral vision
- Faltering weight
- Enlarged liver
- Night blindness
- Short stature
- Progressive muscle weakness
- Elevated levels of phytanic acid
- Very long chain fatty acid accumulation
What is the most extensive membrane system in a eukaryotic cell?
Endoplasmic Reticulum
What’s the importance of the endoplasmic reticulum in transporting proteins?
- Proteins destined for the Golgi apparatus, lysosomes, endosomes, cell surface all first enter the ER from the cytosol
- Once in ER, proteins do not return to cytosol but rather travel via vesicles
- Entry point for proteins destined for other organelles as well as the ER itself
What is distinguishable about proteins entering the endoplasmic reticulum?
Proteins that enter the ER begin to enter the ER membrane before the polypeptide chain has been completely synthesised
What is the importance of the synthesis of proteins encoded by the nuclear genome?
- ribosomes that are translating proteins with no ER signal remain free in the cytosol
- ribosomes that are translating proteins containing an ER signal sequence on the growing polypeptide chain will be directed to the ER membrane
- many ribosomes bind to each mRNA molecule forming a polyribosome; at the end of each round of protein synthesis, the ribosomal subunits are released and rejoin the common pool in the cytosol
Where are soluble proteins made on the endoplasmic reticulum released into?
The endoplasmic reticulum lumen
What two protein components help guide the endoplasmic reticulum signal sequences to the ER membrane?
- a signal-recognition particle (SRP)
- an SRP receptor
What is the function of a signal-recognition particle (SRP)?
it is present in the cytosol and binds to both the ribosome and the ER signal sequence when it emerges from the ribosome
What is the function of an SRP receptor?
It is embedded in the ER membrane and recognises the SRP. The SRP-ribosome complex then binds to an SRP receptor in the ER membrane. The SRP is released, passing the ribosome from the SRP receptor to a protein trans locator in the ER membrane. Protein synthesis resumes and the translocator starts to transfer the growing polypeptide across the lipid bilayer.
What is the function of the protein translocator?
It binds the signal sequence and threads the rest of the polypeptide across the lipid bilayer as a loop
Describe what happens during the translocation process of the protein into the ER lumen
1) At some point during the translocation process, the signal peptide is cleaved from the growing protein by a signal peptidase
2) Cleaved signal sequence is ejected into the bilayer where it is degraded
3) Once the C-terminus of a soluble protein has passed through the translocation channel the protein will be released into the ER lumen and the pore of the translocation channel closes
Which organelles are membrane-enclosed?
- Nucleus
- Endoplasmic reticulum
- Golgi apparatus
- Lysosomes
- Endosomes
- Mitochondria
- Chloroplasts
- Peroxisomes
Which organelles are part of the endomembrane system?
- Endoplasmic reticulum
- Golgi apparatus
- Peroxisomes
- Endosomes
- Lysosomes
What happens to water-soluble proteins destined for secretion or for the lumen of an organelle of the endomembrane system?
It passes completely into the ER lumen
What happens to transmembrane proteins destine for either the membrane of endomembrane system organelles or for the plasma membrane?
They remain anchored in the lipid bilayer by one or more membrane-spanning alpha helices
What happens to proteins in the ER lumen?
- proteins fold up
- assemble with their protein partners
- form disulphide bonds
- become decorated with oligosaccharide chains
Which organelles sorts ingested molecules and recycles some of them back to the plasma membrane?
Endosome
A common pool of ribosomes is used to synthesise both the proteins that stay in the cytosol and those that are destined for the ER (TRUE/FALSE)
TRUE
The movement of materials from the plasma membrane, through endosomes, and then to lysosomes describes which type of pathway?
Endocytotic pathway
