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Questions and Answers

What protein initiates the binding process for COPII vesicle formation at the ER?

Rab Protein

SNAP

Sec23

Sar1-GDP (correct)

Which component is not involved in COPII vesicle formation?

v-SNARE (correct)

GTP

Sec23/24

SEC13/31

How do vesicles that leave the ER typically form?

Through packing of unfolded proteins

Both selective exit signals and bulk flow (correct)

By only the selection of specific proteins

Through a process dependent on random diffusion

What happens to COPII coat proteins after vesicles form?

They are shed from the final vesicles. Signup and view all the answers

Which of the following proteins is a G protein associated with vesicle transport?

Rab Signup and view all the answers

What characterizes the vesicles that are transported from the ER to the Golgi?

They can vary in shape and size. Signup and view all the answers

Which step in COPII vesicle formation involves Sar1 translocating through the ER membrane?

3 Signup and view all the answers

What role do SNARE proteins play in the context of vesicle delivery?

They facilitate the fusion of vesicles with target membranes. Signup and view all the answers

Which of the following statements is true regarding the early endosome?

It is involved in the maturation process of vesicles. Signup and view all the answers

What process is described by the movement of vesicles from the Golgi to the cell exterior?

Exocytosis Signup and view all the answers

What is the function of the rough endoplasmic reticulum (ER)?

Protein production for membrane and extracellular use Signup and view all the answers

Which sequence features in the ER signal sequence help target proteins to the ER?

Hydrophobic regions (H-region) Signup and view all the answers

What occurs during co-translational translocation?

Proteins translocate to the ER during translation Signup and view all the answers

What is the role of calnexin in the ER?

Recognizes misfolded proteins Signup and view all the answers

What happens to misfolded proteins in the ER?

They are exported for degradation in the cytosol Signup and view all the answers

Which of the following is a result of the Unfolded Protein Response (UPR)?

Enhanced expression of chaperone genes Signup and view all the answers

Which protein modification occurs at the Golgi apparatus?

O-linked glycosylation Signup and view all the answers

What class of CFTR mutations leads to misfolded and degraded proteins?

Class II Signup and view all the answers

What is a consequence of defective protein folding in cells?

Pathogenicity and disease development Signup and view all the answers

What is the primary function of the Sec61 complex in post-translational translocation?

Core translocon facilitating protein movement Signup and view all the answers

Which process primarily occurs when proteins are misfolded and accumulate in the ER?

Activation of the Unfolded Protein Response (UPR) Signup and view all the answers

What is a major role of chaperones in the ER?

Assist in protein folding and stabilization Signup and view all the answers

What is the fate of proteins that escape the quality control system in the ER?

They are degraded by the proteosome Signup and view all the answers

What role do SNARE proteins play in neurotransmitter release?

They facilitate the fusion of vesicles with the target membrane. Signup and view all the answers

Which neurotransmitter fusion protein is cut by tetanus toxin?

Synaptobrevin Signup and view all the answers

What is a common symptom of Congenital muscular dystrophy (CMD) caused by a BET1 deficiency?

Low muscle tone Signup and view all the answers

Which of the following describes the process of pinocytosis?

It is characterized by the formation of clathrin-coated pits. Signup and view all the answers

What kind of syndrome is Cranio-lenticulo-sutural dysplasia associated with?

Autosomal recessive syndrome Signup and view all the answers

Which method of endocytosis is characterized by the formation of large fluid-filled vesicles and cell-surface protrusions?

Macropinocytosis Signup and view all the answers

Which protein is known to facilitate the attachment of SNARE complexes to membranes?

NSF Signup and view all the answers

What is the primary function of clathrin in endocytosis?

To form the vesicles for pinocytosis. Signup and view all the answers

What is the role of PI(4,5)P2 in the formation of phagosomes?

It stimulates actin polymerization. Signup and view all the answers

What type of defect is associated with many diseases related to the secretory pathway?

Vesicle fusion defects Signup and view all the answers

Which of the following proteins is involved in vesicle formation in the ER?

Sar1 Signup and view all the answers

Which process involves the engulfing of large particles by extending pseudopods?

Phagocytosis Signup and view all the answers

Which type of secretion is characterized as regulated?

Exocytosis Signup and view all the answers

What is the function of Rab proteins in vesicle trafficking?

They facilitate vesicle fusion with membranes. Signup and view all the answers

What is the primary role of t-SNAREs during vesicle delivery?

To enable membrane fusion. Signup and view all the answers

Which type of endocytosis involves clathrin-mediated pathways?

Pinocytosis Signup and view all the answers

What pathology is associated with defects in vesicle fusion?

Cranio-lenticulo-sutural dysplasia Signup and view all the answers

Which protein complex is primarily associated with COPII vesicle formation?

Sec23/24 Signup and view all the answers

Which signal is recognized by the KDEL receptor for ER protein retrieval?

KDEL signal Signup and view all the answers

What is the primary function of COPI coated vesicles in the secretory pathway?

Carry cargo during retrograde transport from the Golgi to ER Signup and view all the answers

What role do Rab proteins play in vesicle delivery?

They guide vesicles to their target locations Signup and view all the answers

Which of the following is NOT a function of the Trans Golgi Network (TGN)?

Sorting proteins to the Golgi cisterna Signup and view all the answers

What is a characteristic feature of regulated secretion?

Retention of specific cargo until a signal is received Signup and view all the answers

What protein binds to GTP to facilitate vesicle pinching during endocytosis?

Dynamin Signup and view all the answers

Which of the following proteins is targeted with a mannose 6-phosphate tag?

Lysosomal proteins Signup and view all the answers

What type of secretion involves proteins without specific targeting signals?

Constitutive secretion Signup and view all the answers

What is the role of NSF in vesicle transport?

To disassemble SNARE complexes Signup and view all the answers

Which of the following correctly describes COPII vesicle formation?

The coat disassembles after vesicle budding Signup and view all the answers

Which of the following describes a characteristic of the cis Golgi network?

Transitional area between the ER and Golgi Signup and view all the answers

What type of vesicle is primarily involved in transporting materials to the cell surface?

Clathrin-coated vesicles Signup and view all the answers

During vesicle transport, what must occur after the COPI coat assembles on the KDEL receptor?

Vesicle pinches off from the membrane Signup and view all the answers

Which protein is recognized by the dilysine retrieval signal for membrane protein retrieval?

KDEL receptor Signup and view all the answers

Study Notes

Cell Biology Lecture 3: Protein Translocation and the Secretory Pathway

Lecture covered protein translocation and the secretory pathway
Topics included protein targeting, eukaryotic secretory pathway, rough/smooth ER, protein translocation, secretory pathway modifications, quality control, and misfolded proteins.
Misfolded membrane proteins were also discussed, including their pathogenicity.
Learning objectives included understanding differences between rough and smooth ER, co- and post-translational translocation, ER protein modification and quality control; impact of misfolded proteins and cellular pathogenesis.

Protein Translocation and the Secretory Pathway

Lecture covered the structure of a protein and targeting signals
Proteins are made in the cytosol
They are directed to the correct cellular compartment
The lecture focused on the co-translational and post-translational translocation of proteins into the ER.
The pathway includes the ER, Golgi, and other organelles.
Protein targeting is crucial for protein function

Protein Targeting

Most proteins are made in the cytosol.
Proteins need to be directed to their correct cellular compartment for proper function.
This lecture covered the mechanisms for directing proteins to specific locations, such as the nucleus, mitochondria, peroxisomes and the ER.
Most protein translocation in humans is co-translational.

Eukaryotic Secretory Pathway

Proteins destined for secretion or insertion into membranes follow a pathway beginning in the ER.
The pathway continues through the Golgi apparatus and other organelles before reaching the cell exterior.
Most secretory proteins are co-translationally targeted in humans to avoid potential aggregation issues.

Rough/Smooth ER Recap

Rough ER is studded with ribosomes, essential for protein production
Smooth ER is involved in lipid processing and secretion
Both are critical parts of the secretory pathway

Protein Translocation

Protein translocation is how proteins are moved across membranes.
Co-translational translocation involves ribosomes translating mRNA into protein while simultaneously moving the protein into the ER membrane as it's being synthesized.
Post-translational translocation involves already synthesized proteins being transported into the ER membrane.

Secretory Pathway Modifications

Proteins undergo modifications like glycosylation, proteolytic cleavage, oligomerization, and disulfide bond formation.
These modifications are vital for protein function and quality control

Quality Control & Misfolded Proteins

Cells monitor protein folding.
If misfolded, chaperones may help refolding or target the protein for degradation by the proteasome.
Chaperone proteins assist in proper folding and quality control.
They facilitate proper folding and help prevent aggregation of misfolded proteins.
Calnexin recognizes misfolded proteins

Misfolded Membrane Proteins – Pathogenicity

Misfolded membrane proteins can lead to diseases like cystic fibrosis (CFTR) - related to protein dysfunction affecting ion transport.
Other potential disorders include Insulin-resistant syndrome and Autosomal Dominant Deafness type 2A (KCNQ4 mutations).

Protein Translocation in Summary

Protein targeting signals direct proteins to the appropriate location.
Co-translational translocation happens in the ER
Post-translational translocation also happens
Misfolded proteins are recognised by chaperones like calnexin and are tagged for degradation, if necessary
Improper folding or trafficking can lead to disease

The Secretory Pathway

The pathway transports various molecules within and outside the cell
Exocytosis describes how substances are actively transported out of the cell.
Endocytosis describes how substances are transported into the cell.
Different types exist including pinocytosis, clathrin independent and dependent; and phagocytosis.

Exocytosis - Types of Secretion

This section outlined two types of exocytosis
Constitutive secretion is a continuous process where proteins are exported.
Regulated secretion involves storing proteins in vesicles and releasing them in response to signals.

Neuronal Synapse Vesicle Delivery

This section focused on how vesicles carrying neurotransmitters are targeted and released to the synaptic cleft for communication between neurons.
The SNARE proteins play a critical role in vesicle fusion to the target membrane.

Toxins on Vesicle Fusion

Specific toxins interfere with the process of vesicle fusion and potentially with disease.

Endocytosis: Transport Pathways

Several endocytic pathways exist
Endocytic pathways are involved in bringing materials into the cell.
The processes involved in endocytosis include pinocytosis, macropinocytosis, receptor-mediated endocytosis, and phagocytosis.

Endocytosis - Types

This section detailed the various mechanisms underpinning endocytosis
Pinocytosis is a method for consuming fluid or small molecules through invagination of the plasma membrane.
Receptor-mediated endocytosis is a highly specific process where receptors on the cell surface bind to specific ligands in the extracellular fluid, causing the formation of a clathrin-coated pit that eventually pinches off as a coated vesicle to deliver its cargo.
Macropinocytosis involves large, non-selective intake of extracellular fluid and material.
Phagocytosis is when the cell engulfs large particles like bacteria.

Golgi Trafficking - The Golgi

The Golgi apparatus is critical for modifying, sorting, and transporting proteins and other molecules throughout the secretory pathways.
The Golgi comprises different compartments like cis, medial, and trans cisternae.
Different proteins are modified and sorted across these compartments to their targeted destinations.

Golgi to ER Movement

Proteins within the ER may need to be retrieved
The process uses COPI-coated vesicles to carry cargo
KDEL receptors recognise specific retrieval signals on cargo proteins in the cis and medial Golgi.
The vesicles then return the proteins to the ER.

ER/Golgi Trafficking - Vesicle Formation

COPII proteins direct vesicles carrying cargo from the ER to the Golgi.
Multiple steps are involved including GTP binding, signal exposure, and insertion into the ER membrane for transport to the Golgi.
The mechanisms used for vesicle formation and maintenance of cell size are critical for cellular function.

The Secretory Pathway Summary

Lecture highlights the various parts of the secretory pathway, including transport vesicle formation, delivery, and modifications.
A combination of endocytosis and exocytosis allow for efficient movement of materials into and out of the cell.
The pathways' regulation is essential to maintain healthy cellular function.

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