Retta - L6 part 1

Questions and Answers

What do ERM proteins primarily mediate the interaction between?

Mitochondria and endoplasmic reticulum

Nucleus and cytoplasm

Intracellular vesicles and Golgi apparatus

Actin cytoskeleton and plasma membrane (correct)

Which proteins make up the ERM protein family?

Ezrin, radixin, and moesin (correct)

Krit 1, gelsolin, and FERM

Vimentin, keratin, and collagen

Actin, myosin, and tubulin

What domain do members of the FERM protein family share?

FERM domain (correct)

SH3 domain

PH domain

PDZ domain

What triggers the activation of ERM proteins?

Receptors binding to specific signaling molecules Signup and view all the answers

What structural change occurs in ERM proteins to enable their activity?

Intramolecular interaction between N terminal and C terminal Signup and view all the answers

What role does Formin play in actin filament formation?

It promotes the elongation of straight filaments and nucleation of actin. Signup and view all the answers

What is one of the diseases associated with mutations in formin genes?

Sensorineural hearing loss Signup and view all the answers

Which actin-nucleating factor is responsible for generating branched filaments?

Arp2/3 Signup and view all the answers

How do formin family proteins stabilize actin dimers and trimers?

By encircling them with their dimeric formin homology 2 domains. Signup and view all the answers

Which of the following is NOT a condition associated with mutations in formin genes?

Osteoporosis Signup and view all the answers

What is a primary function of actin-nucleating factors for cellular structure?

To accelerate polymerization and support structural integrity. Signup and view all the answers

Which gene was the first identified mutation affecting formin?

DIAPH1 Signup and view all the answers

What potential impact do alterations in formin genes have beyond primary genetic diseases?

They can lead to various developmental defects and cancers. Signup and view all the answers

What is the primary role of CDC42 in cell protrusions?

Promotes filopodia formation Signup and view all the answers

Which GTPase is primarily responsible for the formation of lamellipodia?

RAC Signup and view all the answers

What structural role do stress fibers play in cellular function?

Promote cell contractility and adhesion Signup and view all the answers

What mechanism is involved in the interaction between actin filaments and myosin in stress fibers?

Sliding filament mechanism Signup and view all the answers

What can be inferred about the signals that affect the organization of the actin cytoskeleton?

They vary depending on environmental conditions. Signup and view all the answers

Which of the following is NOT a member of the RHO family GTPases mentioned?

K-RAS Signup and view all the answers

How do stress fibers contribute to cell migration?

By promoting extension and retraction of the cell Signup and view all the answers

What characteristic differentiates filopodia from microvilli?

Filopodia are irregular and elongated protrusions. Signup and view all the answers

What significance do the stress fibers have related to cell attachment?

They are fundamental for tight attachment to a substrate. Signup and view all the answers

Which structure is formed by the interaction of actin filaments and myosin in the cleavage furrow?

Contractile ring Signup and view all the answers

What effect does cofilin have on actin filaments?

It destabilizes actin filaments, causing them to twist more tightly. Signup and view all the answers

Which protein is primarily involved in the severing of actin filaments?

Gelsolin Signup and view all the answers

How does the presence of calcium affect Gelsolin's activity?

It promotes Gelsolin's activation by changing its conformation. Signup and view all the answers

What is a consequence of Gelsolin cleaving actin filaments during apoptosis?

Disassembly of the cytoskeleton leading to membrane blebbing. Signup and view all the answers

What role does tropomyosin play in muscle contraction?

It stabilizes actin filaments along with troponin. Signup and view all the answers

Which actin filament-associated structures are involved in enhancing the cell's surface for nutrient absorption?

Microvilli Signup and view all the answers

What are proteins that promote the formation of bundles called?

Bundling proteins Signup and view all the answers

How does the binding of cofilin to actin influence the actin filament structure?

It causes the actin filament to collapse into a compact structure. Signup and view all the answers

Which proteins are known to contribute to the formation of gel-like networks?

Filamin and spectrin Signup and view all the answers

What is the stoichiometry of cofilin binding to actin subunits?

1:1 Signup and view all the answers

Which of the following is NOT a function associated with actin filaments?

Regulating apoptosis directly. Signup and view all the answers

What role does myosin play in relation to actin filaments?

Enables reciprocal sliding of filaments Signup and view all the answers

Which factor influences the stability of actin filaments bound to ADP?

Cofilin binding to actin filaments. Signup and view all the answers

How does fimbrin promote the formation of parallel bundles?

By connecting filaments with a small distance due to its size Signup and view all the answers

What distance does alpha-actinin maintain between parallel actin filaments?

30 nm Signup and view all the answers

What is the significance of the cross-linking formed by filamin?

It creates a network of actin filaments Signup and view all the answers

What type of structure does spectrin promote in cells?

Gel-like networks Signup and view all the answers

Which statement about actin-binding sites is true?

Two binding sites are required for cross-linking Signup and view all the answers

How do stress fibers contribute to cell behavior?

They promote cell contraction Signup and view all the answers

Study Notes

Cytoskeleton Overview

Actin-nucleating proteins play crucial roles in actin filament formation, with Formin promoting straight filaments and Arp2/3 generating branched filaments.
Formin stabilizes actin dimers and trimers using formin homology 2 domains, facilitating nucleation and elongation of filaments.

Mutations in the DIAPH1 gene, linked to sensorineural hearing loss, were among the first identified affecting formin.
Alterations in additional formin family genes can cause diverse diseases, including intellectual disability, renal disease, cardiomyopathy, and primary ovarian insufficiency.

Actin Filament Regulation

Proteins that interact with actin filaments can either stabilize or destabilize them; cofilin destabilizes by twisting filaments, while tropomyosin stabilizes filaments and collaborates with troponin in muscle contraction.
Cofilin's small size (14 kDa) allows it to bind in a 1:1 ratio with actin, enhancing disassembly, particularly in ADP-bound regions.

Severing Proteins and Actin Dynamics

Gelsolin is a calcium-regulated severing protein that fragments actin filaments, facilitating rapid depolymerization and cytoskeletal remodeling.
In apoptosis, Caspase-3 activates Gelsolin by cleaving it, allowing it to disassemble actin filaments independently of calcium, contributing to apoptotic cell death.

Functions of Actin Filaments

Actin filaments support structures like microvilli, enhancing absorption in intestinal epithelial cells.
They form adhesion belts for intercellular connections and provide structural support to the plasma membrane.
Filopodia and lamellipodia are actin-driven membrane protrusions; filopodia are elongated while lamellipodia are broader extensions at the leading edge of migrating cells.

GTPase Regulation of Actin Structures

Small GTPases from the RHO family, such as CDC42 and RAC, regulate actin dynamics; CDC42 promotes filopodia formation, while RAC favors lamellipodia and branched networks.
RHOA is another GTPase involved in generating stress fibers, essential for cell contractility and migration.

Contractility and Cell Movement

Stress fibers are parallel bundles of actin linked by accessory proteins, facilitating cell contractility through interactions with myosin-2 filaments.
In cytokinesis, contractile rings made of actin and myosin facilitate the separation of daughter cells during cell division.

Accessory Proteins in Actin Structure

Proteins like fimbrin and α-actinin promote the formation of parallel actin bundles, while filamin and spectrin contribute to gel-like networks.
Fimbrin, a monomer, creates closely spaced bundles, while α-actinin, a dimer, allows greater distances for myosin interaction, enhancing contractility.

Gel-like Structures and Cellular Shape

Filamin and spectrin's cross-linking abilities create networks crucial for maintaining cell shape, particularly in red blood cells.
Alterations in these proteins can lead to diseases, including conditions affecting blood cell shape and function, like anemia.### ERM Proteins and Actin Cytoskeleton Interaction
ERM proteins (ezrin, radixin, moesin) mediate the interaction between the actin cytoskeleton and the plasma membrane.
They are characterized by the FERM domain, consisting of three lobes (F1, F2, F3), essential for their function.
Krit 1 protein, linked to cerebral cavernous malformation, also contains the FERM domain, showcasing structural similarities.

FERM Protein Family

The family includes ERM proteins and Bond 4.1, all sharing the distinct FERM domain.
The FERM domain assists in linking cytoskeleton components with plasma membrane structures.

Actin Filament Formation

Actin filaments form selectively at the plasma membrane based on specific signaling events.
Signaling molecules activate transmembrane receptors, which in turn trigger ERM proteins from an inactive to an active state.

Mechanism of ERM Protein Activation

ERM proteins typically exist in a closed conformation due to intramolecular interactions between their N-terminal and C-terminal regions.
Activation requires a signal that induces a conformational change, allowing the proteins to interact with actin and the plasma membrane.

Role in Cell Movement

Activated ERM proteins facilitate the interaction between actin filaments and plasma membrane, essential for cell structures like filopodia and lamellipodia.
Specific signals dictate the formation and elongation of actin filaments at designated locations on the cell surface, influencing cellular responses.

Summary of Signal Transduction

Signal transduction involves cell surface receptor activation, leading to ERM protein activation.
This precise interaction is critical for spatially regulated actin polymerization and cellular dynamics.

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Description

Test your knowledge on the cytoskeleton, focusing on actin-nucleating proteins like Formin and Arp2/3. Learn about their roles in actin filament formation and the implications of mutations in related genes leading to various human diseases. This quiz will deepen your understanding of actin filament regulation and its significance in health.