Intracellular Compartments And Protein Transport Flashcards
Internal membranes
In eukaryotic cells, internal membranes create enclosed compartment that segregate different metabolic processes
Eukaryotic cells
Contain a basic set of membrane enclosed organelles (intestinal cell)
Protein following
Proteins in different cellular compartments and structures can be followed by green fluorescent protein tagging
GFP
Tagging a protein with GFP allows the resulting fusion to be tracked throughout the cell
Relative ratio of intracellular compartments
Varies depending on the cell type and it’s function
Hepatocytes
. Hepatocytes are the main cell types in the liver
Hepatocytes are the principle sites of production of lipoprotein particle (carry lipids via blood stream to other parts of the body)
Hepatocytes are involved in detoxification lipid soluble drugs and various harmful compounds by metabolism
Membrane-enclosed organelles import proteins by one of tree mechanisms
- Transport through nuclear pores (gated)
- Transport across membranes (membrane)
- Transport by vesicles (vesicular)
Gated
Cytosol-nucleus
Transmembrane
Cytosol- Mitochondria;peroxisome;plastids;ER
Vesicular
ER- golgi
Golgi-secretion vesicles; lysosome; endosome; cell exterior
Signal sequences
Direct proteins to the correct compartment
Often found at the N-terminus
Specialized signal peptidases remove the signal sequence from the finished protein once the sorting process is complete
Is the signaling finished the signal sequence get a signal patch
Nucleolus
Is a ribosome-producing factory
Cajal bodies
Are regions within the nucleus that are enriched in proteins and RNAs involved in mRNA processing
They are the main sites for the assembly of small nuclear ribonucleoproteins (snRNPs)
PML / promyelocytic leukaemia
Spherical structure in the nucleus
The principal organizing component of PML bodies is the PML protein
Vary in composition and have been implicated in cellular processes such as telomere lengthening and the DNA damage response
Nuclear speckles
Intrachromatin granule cluster
Nuclear domains enriched in pre mRNA splicing factors
Located in the interchromatin region of the nucleoplasm
Evolving of nuclear membrane and ER
May have evolved through invagination of the plasma membrane
Nuclear pores
Proteins enter the nucleus through nuclear pores
The inner and outer membran of the nucleus contain different protein compositions
The inner nuclear membran contain specific proteins that act as anchoring sites for chromatin and nuclear lamina
The outer membran is continuous with the membrane of the ER
Nucleoporin
Nuclear protein complexes are formed by about 30 different protein called, nucleoporins
and perforate the nuclear envelope
Nuclear lamina
Form of intermediate filament that gives structure, shape and strength to the nucleus
LMNA gene- code for A and C type nuclear lamina
LMNB gene- code for B type nuclear lamina
Mesh like structure
An attachment site for chromatin and chromatin binding proteins for regulating gene expression
Mutations in lamin proteins
Cause laminopathies
“Progeria” - a rare class of premature aging disorder
Hutchinson gilford progeria syndrome (HGPS)
Nuclear pore complexes (NPC)
The transport of molecules between the nucleus and the cytosol are the nucleus and the cytosol communicate with each other through NPC - gate transport
Gated transport
Bidirectional traffic at the nuclear envelope: import and export
Water soluble can diffuse passively through aqueous passages at nuclear pore complex
GTP hydrolysis
Energy supplied by GTP hydrolysis drives nuclear transport
Monomerik GTPase =RAN
NBS(nuclear export signal)
Peroxisomes
Contain oxidative enzymes (oxidase and catalase)
Involved in oxygen utilization
Name came from hydrogen peroxidase
- Peroxisomes in liver and kidney cells detoxify blood (Alkohol, organic contaminants)
- Involved in breakdown of fatty acids to acetyl CoA (Beta oxidation)
- Catalyze plasmalogen synthesis particularly important for myelination of neurons
A short signal sequence directs the import of proteins into peroxisomes
Peroxins
Participate in import that requires ATP hydrolysis
Reside on the peroxisome membrane and participate in ATP driven importing of peroxisome resident proteins and enzymes ATP hydrolysis
Peroximal disorders
Disorders of Peroxisome biogenesis
Single peroxisomal enzyme/ protein deficiencies
Disorders of Peroxisome biogenesis
Zellweger syndrome!
Neonatal adrenoleukodystrophy
Hyperpipecolic acidaemia
Single peroxisomal enzyme/ protein deficiencies
X-linked adrenoleukodystrophy
Acryl-CoA oxidase deficiency
Zellweger Syndrom
Is related to peroxisome biogenesis disorder PBD -leukodystrophies
Damage the white matter of the brain and also affect how the body metabolizes particular substance in the blood and organ tissue
Enlarged liver
Increased of copper and iron in the blood
Inability to move
Intellectual disability
Gastrointestinal bleeding prenatal growth failure
Endoplasmic reticulum
Endo=within/plasmic=the cell/reticulum=net
rER = ribosome associated ER
sER = specialized in Lipid metabolism
- transitional ER = area of smooth ER from which transport vesicles carrying newly synthesized proteins and lipids bud off for transport to Golgi
-sarcoplasmic Reticulum specialized type of smooth ER that regulate the calcium ion concentration in the cytoplasm of striated muscle cells
Function of ER
- Central role in protein and lipid biosynthesis
- Provides the space for Ca storage
- All transmembrane proteins and secreted proteins pass through the ER lumen
- Polypeptide chain are folded and assembled in the lumen of rough ER , disulfide bonds are formed, incorrectly folded proteins are recognized
sER-lipid biosynthesis of phosphogliserid,phosphatidylserin, cholesterol,seramide are carried out (!spingolipids in golgi, cardiolipin in mitochondria!)
Function of sER
Function in several metabolic processes
-synthesis of lipids and steroids
-metabolism of carbohydrates
-attachment of receptors on cell membrane proteins, and steroid metabolism
!drug metabolism- some drugs are modified by microsomal enzymes -cytochrome P450
-contain the enzyme glucose6phosphatase
Molecular function of the rER
Translocation Export ERAD ER stress signaling Ca homeostasis Disulfide isomerase N linked glycosylation
Protein folding
Protein fold into a conformation of lowest energy
Molecular chaperons often assist in protein folding
Chaperone proteins
Act as isolation chambers that help a polypeptide
Other chaperon proteins act as isolation chambers that help a polypeptide fold
Prevent misfolded or partially assembled proteins from leaving the ER
Proteosome
Misfolded or unwanted proteins are proteolytically cleaved by the proteasome
Like a small garbage-destruction machi
Small protein called ubiquitin form polyubiquitin chain by specifically binding lysines
Modify and mark proteins mostly for degradation by proteosome
Disulfide bridge
Are formed in the rER by protein disulfide isomerase (PDI)
Disulfide bonds help to stabilize extracellular proteins
N linked oligosaccharide
Most proteins synthesized in the rER are glycosylated by the addition of a common N linked oligosaccharide
Transport from cytosol to ER
Through transmembrane transport
Co translational process
Mammalian cells begin to import most proteins into ER before complete synthesis of the polypeptide chain
Pool of ribosomes
A common pool of ribosomes is used to synthesis all the proteins encoded by the nuclear genome
Membrane-bound polyribosomes
. can translate mRNAs encoding ER proteins
Signal recognition particle
An ER signal sequence and an SRP direct a ribosome to the ER membrane
Start and stop signals
Start and stop signals determine the arrangements of a transmembrane protein in the lipid bilayer
Signal sequence- trigger the opening of the pore in the protein translocator
Single pass transmembrane
A single pass Tran protein is retained in the lipid bilayer
Double pass transmembrane
A double pass transmembrane protein has an internal ER signal sequence
Unfolded protein respon UPR
Misfolded proteins in the ER activate an unfolded protein response
Chaperones prevent misfolded pr partially assembled proteins from leaving the ER
ER induced stress in inflammation
Affect pancreatic beta cells as well as adipocytes and macrophages
Cancer cystic fibrosis
Environmental or genetic factors of ER stress
Proteins folding incorrectly
Alzheimer Parkinson Cancer Obesity Diabetes
Golgi Apparatus sides
Cis - facing to ER
Trans - facing to membrane
Function of golgi
Lipid biosynthesis and maturation (sphingolipin)
Carbohydrate synthesis and o linked glycosylation
Formation of secretary vesicles and secretion
Sulfation(give neg charge-> interaction with other…)
Addition of mannose6phosohate to lysosomal protein(with them can go to lysosome)
Storage of protein lipoid material
Glycosylation
Proteins and lipids are further modified by mostly glycosylations in the Golgi apparatus
Lysosome
Contains a large variety of hydrolytic enzymes, which are only active under acidic conditions
H pumps make the inside of the lysosome acidic 5.0
Materials destined for degradation in lysosomes follow different pathways to the lysosome
!autophagy!= degradations for obsolete parts of the cell- the cell literally eats itself
Lysosomal storage Diseases
No digestion => storage!
Fabry disease Gaucher disease Mucopolysaccharidosis Niemann pick c disease Tay sachs diseases Metachromatic leukodystrophy and Krabbe disease
Life cycle of M.tuberculosis
Inhaled by aerosols
Transmitted to the lungs
Phagocytozed by macrophages
Apoptosis
Vesicular Transport Nobel price
James rothman, randy schekman, Thomas Sudhoff have discovered the molecular principles that govern how this cargo is delivered to the right place at the right time in the cell
Vesicular transport
Distrubances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes and immunological disorders
Vesicle budding and fusion
Occur during vesicular transport
Budding vesicle with contents selected for transport
Function
Carry soluble proteins and membrane between compartments
Bud from one membrane and dude with another carry membrane components and soluble proteins between compartments of the endomembrane system and the plasma membrane
Exocytosis
Delivery of newly synthesized proteins, lipid and carbohydrates to either plasma membrane or extracellular space
Endocytosis
Removal of plasma membrane components, capture important nutrients deliver them to the internal compartment
