Cell structure and function 2 Flashcards
Describe the structure and function of nuclear envelope and nuclear pore complex
The above diagram shows the structure of a typical nucleus.
The nucleus is encapsulated by a nuclear envelope. It helps to mediate trafficking between cytoplasm and nucleoplasm, regulating interactions with DNA and ensure the stability of the genome. The nuclear envelope is a double-membrane structure, made from phospholipids. The inner membrane faces the nucleoplasm, and the outer membrane is continuous with the endoplasmic reticulum.
The key role of the nuclear envelope is to regulate transport between the cytoplasm and the nucleus.
Entry and exit from the nuclear envelope occurs via nuclear pores. These ensure that the right moelcules enter and the ‘wrong’ molecules stay out.
The pore is composed of a complex assembly of proteins; it traverses the nucelar membrane and forms a commuication cahnnel between nucleoplasm and cytoplasm.
The pore complex is 50 nm wide, and approximately 500 proteins ar involved in its formation.
Key imports to the nucleus include histones, TFs and enzymes. Key exports are mainly RNA transcripts ^[note that pores can control speed of export and consitute a regulator of gene expressin kinetics]. There is a fraction of small molecules that diffuse freely across the nuclear pore.
Describe pathologies underlined by abnormalities in nuclear envelope or nuclear pore complex
Maintaining the integrity of the nuclear envelope is key to health. Thus, gene mutations affecting the structure of proteins involved in nuclear pore assembly can have serious consequences.
Examples include Progeria or Hutchinson-Gilford syndrome, a disease of accelerated aging evident at 1 year old, caused by a mutation of the lamin A gene ^[encodes for protein necessary to hold the nucleus together i.e. a part of the nuclear lamina, providing shape and stability to the inner nuclear membrane ]
Note that many viruses use the nuclear pore complex to gain access to the transcriptional machinery of the cell in order to replicate ([[Microbiology Lecture 2]]). ^[the proteases used by viruses to alter NPCs a potential target of antivirals: see also : https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwiYwb7Esvj9AhXC6jgGHTYNCosQFnoECBEQAQ&url=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC8073804%2F&usg=AOvVaw3OLuXfhtSn-WKgIf9a7_v-]
Maintaining the integrity of the nuclear envelope is essential. However, there are instances where disassembly of the nuclear envelope must occur i.e. during cell division.
The nuclear pore complex must be deconstructed and reconstructed each time the cell divides. The nucleus is anchored to the cytoskeleton by structural proteins ([[Genetics Lecture 2]], [[Cell Biology Lecture 3]]) that send signals related to the state of DNA i.e. how condensed it is, and work to align the chromosomes in mitosis.
Describe the ER
The endoplasmic reticulum or ER is a network of interconnected tubules connected to the nuclear membrane (outer) and extending into the cytoplasm. It is enclosed by a membrane, and contains folded and flattened regions called cisternae.
There are two types of ER or region of ER and they include smooth ER, and rough ER. The key difference between them is the association of ribosomes on the rough ER (rER).
The key roles of the ER include synthesis of proteins, lipids and carbohydrate processibg.
Describe ribosomes and the stages of translation
Ribosomes are the translational machinery of the cell i.e. the site of protein syntesis in the cell. It is located in the cytoplasm and found predominantly on the rER proximal to the nuclear function ^[ i.e.. location related to function. Recall (from years back) free and bound ribosomes].
The ribosome captures the mRNA exiting through the nuclear pore complex and translates it into a protein. The ribosome is comprised of two subunits a large 60S and a small 40S. The ribosomal subunits incorporate rRNA and structural proteins.
Note: the ribosomes are not enclosed by a membrane.
This diagram shows the structure of tRNA. It has a secondary structure. Note the base loop has an ‘anticodon’, this is used to match the amino acid to its respective codon inthe mRNA sequence.
The three main stages of translation include:
- Initiation: an enzyme (aminoacyl tRNA synthase) conjugates an amino acid to a tRNA (that corresponds to a codon on the mRNA). The tRNA-Met binds to the P site
- Elongation i.e. peptide bond formation. The incoming aminoacyl-tRNA binds to A site using complementary base pairing. The amino acid residue on the aminoacyl RNA forms a peptide bond with the amino acid at site P. This is either the initial tRNA-Met, or a growing peptide
- Translocation: The ribosome moves along the mRNA emptying site A, exposing it for the binding of a new aminoacyl tRNA. The shifting of the ribosome is mediated by elongation factors or ribozymes ^[enzymes made from RNA as oppose to AAs]
Describe the movement of ribosomal subunits
The ribosomal subunits can detach, migrate inside the nucleus pick up and bring out mRNA. The small and large subunits migrate independently outside the nucleus voa nuclear pores, and assemble outside the cytoplasm.
Describe antibiotics can target ribosomes
ribosomes are required for life, and thus its structure across organisms is largely conserved. However there are small differences between eukaryotic and bacterial ribosomes that can be exploited i.e. using antibiotics with no effect on us. It stalls translation, leading to not proteins being produced, which kills cells. ^[note with resistance, bacteria can find another way to translate]
Examples include Macrolides for 50s
aminoglycosydides and tetracucines for 30s
Describe the smooth ER
The smooth ER (sER) is a network of tubular membranes. The complexity and abundance of the sER is cell specific. For example, liver cells have highlyd eveloped sER.
There are many functions of the sER, including:
- synthesis of cholesterol, steroids and lipids ^[([[Biochemistry Lecture 4]])] (required for making cellular membranes)
- metabolism of carbohydrate and detoxification of alcohol and drugs: especially the conversion of glycogen to glucose ([[Biochemistry Lecture 3]])
- major role in detoxification: the addition of a hydroxide molecule, OH-, a number of organic chemicals converting them to safer water-soluble products
Describe the Golgi complex and its role in cell communication
The Golgi complex is the post office of the cell: it tags proteins for delivery throughout the body.
The Golgi complex has two main functions:
- cargo sorting
- glycosylation– the addition of sugars to proteins ([[Biochemistry Lecture 3]])
It is an organelle composed f may membranous sacs and vesicles. It works in concert with the ER and has a similar structure. The membrane of the Golgi protects it from enzymes and the extracellular environment.
Golgi apparatus has two faces: the cis face points towards the ER and the trans face points towards the plasma membrane.
The Golgi apparatus is part of a communication network between myokines and organs –> myokines and brains
There are lots of m proteins in the brain
This mechanism is enhanced with acute exercise.
