Question

Predict how modifications to cellular components (mitochonria, golgi, smooth ER, roigh ER, ribosomes, and cytoskeleton) would alter cellular processes.  

Illustrate how various types of proteins (proteins with different destinations) are made, processed, and excreted or broken down by a cell.

i only need the second one answered

Answer 1

1. Impairment of cellular components.

Mitochondria: Modification will prevent ATP production and oxidative phosphorylation or cellular respiration.

• The mechanism of oxidative phosphorylation occurs in mitochondria of live cells.
• Electrons are transported across various components of electron transport chain (ETC), resulting in series of oxidation-reduction reactions within the inner membrane bound complexes in mitochondria (complex I, II, II, IV).
• ATP synthase complex, designated as F₀F₁- ATP synthase, is located within the mitochondrial cristae.

Golgi apparatus: Modification will impair ptotein trafficking anf transport of cellular components.

• Golgi apparatus, Golgi complex or Golgi body comprise of series of flattened stacked pouches called cisternae.
• After protein synthesis, are targeted for secretory pathway involving movement and modification of proteins, the cis-face of Golgi network receives the protein, followed by trans-face.
• Where the proteins are modified, packaged and finally transported to cell membrane for release or functioning in cell.

Smooth Endoplasmic reticulum: Modification will affect cellular transport, cholesterol synthesis for membranes.

• Forms cellular skeletan and helps in compartmentalization of cell.
• De Novo biosynthesis of steroid, like cholesterol occurs in the smooth endoplasmic reticulum, as it contains the major enzymes required for the synthesis of membrane.
• The secretory pathway involves the movement and modification of proteins through specific membrane bound organelles and vesicles: like, from endoplasmic reticulum lumen, through transport vesicles, to cis-Golgi network, followed by trans-Golgi network.

Rough ER: modification may impair protein synthesis.

• Ribosomes may be attached to Endoplasmic reticulum forming Rough ER.
• They participate in process of translation and help to synthesize proteins.

Cytoskeletons: Modification will impair cellular movements and support.

Cytoskeletons comprises of:

1. Microfilaments or actin filaments-help in rigidity and cellular movements. It is narrowest among microfilaments.
2. Intermediate filaments- bears tension, helps to support the cell junctions and extracellular substances. It is intermediate in size
3. Microtubules- form track for vesicle movements.

Protein modifications:

• After translation process in ribosomes, the polypeptide chain generated undergoes several post-translational modifications and changes and are translocated to other area of the cell or secreted out of the cell, by the process of protein trafficking.
• The proteins are recognized by a short signal sequence (6-12 amino acid sequence) present at the N-terminus, and are targeted to specific organelles, including endoplasmic reticulum, Golgi apparatus, lysosome, by protein targeting.
• While some proteins are not associated with the signal peptide.

a. Lysosome targeting of protein occurs in Cis- Golgi network (CGN).

• N-Acetyl glucosamine (NAG) phosphorylases, first binds to Mannose residues.
• The NAG part is then removed, and Mannose -6- phosphate (M-6-P) is retained on the N-linked oligosaccharide.
• Mannose phosphorylation of proteins is the indication of protein transportation to lysosome.
• Phosphorylated protein is recognized by M-6-P receptor on trans- Golgi network (TGN), and these proteins are directed to lysosome. Signal patch on lysosome recognizes the M-6-P related protein.

b. Proteins are transported through protein coated membrane vesicles, like clathrin-coated, COPI coated, COPII coated. Some protein-cargos may be returned to the E.R, because of the presence of specific signal sequences, that interact with COPI or some other associated proteins.

• If the cargo-protein needs to be retained back to the E.R, it need specific sequence called retrieval signals to be added to their C-terminals.
• The E.R membrane proteins also contain these signal sequence at the C-terminal ends.
• The sequence for E.R resident protein is Lys-Lys-XX, and for soluble E.R protein is Lys—Asp-Glu-Leu and are designated for receptors called KDEL receptors or multi-pass trans-membrane protein. They can interact with COPI.
• Thus, addition or modification of C-terminus of the protein to generate a KDEL signal sequence will retrieve or retain the cargo-protein to E. R. instead of lysosome.

c. Nuclear localization sequence (NLS) allows the protein to be transported to the nucleus.

• NLS sequences are short sequences of about 6 to 8 amino acids, with arginine and lysine amino acids (basic or positive charged). These sequences can associate with nuclear transport receptors (TRs) and helps in transport of cytosolic protein through nuclear membrane pores.
• NLS sequences should be located with the protein, as internal sequences, and not as terminal sequences. Thus, the transport to nucleus may be inhibited, due to adding NLS at C-terminus.
• Proteins or polypeptides associated with the signal peptides: These are transported to nucleus, mitochondria or chloroplast.
• These peptides are usually translated in ribosomes associated with endoplasmic reticulum (RER).
• They contain N-terminal signal peptide.

• The signal sequence also contain more sequences like Start and stop sequences, spanning regions, GPI anchoring regions.
• For targeting to mitochondria, proteins contain N-terminal pre-sequence or matrix targeting sequence.
• This is composed of alternating charged and hydrophobic amino acid residues.
• These amino acids form an amphipathic helix that can target protein translocation across mitochondrial membranes and into the mitochondrial matrix.