Annexe: Growth Cone and Axon Guidance

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Questions and Answers

What is the primary function of the 'navigator' component of the growth cone?

  • Maintaining growth cone movement
  • Providing traction for forward movement
  • Structuring the cytoskeletal framework
  • Translating environmental signals into directional movement (correct)

What is the role of the 'vehicle' component of the growth cone?

  • Receiving signals from the environment
  • Guiding the growth cone towards its target
  • Providing structural support and movement (correct)
  • Responding to environmental cues

What is a 'chemotropic cue' in the context of axon guidance?

  • A chemical signal that attracts or repels the growth cone (correct)
  • A motor protein that drives the growth cone's movement
  • A physical barrier that the growth cone must navigate around
  • A structural component of the growth cone

Why is the dynamic behavior of the growth cone essential for axon guidance?

<p>It enables the growth cone to respond to changing environmental conditions (A)</p> Signup and view all the answers

What is the 'protrusion' stage of growth cone progression?

<p>The stage where the growth cone extends its filopodia (C)</p> Signup and view all the answers

What are the 'intracellular signaling elements' referred to in the context of the growth cone?

<p>The proteins and pathways that transmit signals within the growth cone (C)</p> Signup and view all the answers

Why is the growth cone considered a 'navigator' in axon guidance?

<p>It allows the growth cone to sense and respond to its environment (D)</p> Signup and view all the answers

What does the 'navigator' function of the growth cone depend on?

<p>The specific receptors that are engaged and the internal signaling pathways (B)</p> Signup and view all the answers

What is the primary role of GEFs in the Rho GTPase activation-inactivation cycle?

<p>They promote the binding of GTP to Rho GTPases. (B)</p> Signup and view all the answers

How does activation or inactivation of cytoskeletal effectors influence growth cone steering?

<p>It alters the localization of Rho GTPases, leading to varied responses. (B)</p> Signup and view all the answers

Which statement best describes the role of the Arp2/3 complex in the growth cone?

<p>It is involved in the nucleation of actin filaments. (C)</p> Signup and view all the answers

What is the significance of F-actin retrograde flow towards the C domain of the growth cone?

<p>It is involved in the disassembly of actin filaments at the T zone. (C)</p> Signup and view all the answers

Which of the following is considered a key regulator of F-actin polymerization at the leading edge?

<p>ENA/VASP (B)</p> Signup and view all the answers

How do GAPs contribute to the regulation of Rho GTPases?

<p>They inactivate Rho GTPases by promoting GDP binding. (B)</p> Signup and view all the answers

Which of the following is NOT a direct or indirect downstream effector of Rho GTPases?

<p>UNC5 (A)</p> Signup and view all the answers

What is the primary role of F-actin assembly at the periphery of the growth cone?

<p>It allows for the extension and formation of filopodia. (D)</p> Signup and view all the answers

What is the function of the F-actin network in a growth cone?

<p>To generate force for the growth cone's movement (A)</p> Signup and view all the answers

How does the engagement of myosin II affect the growth cone?

<p>It slows down the retrograde flow of F-actin. (A)</p> Signup and view all the answers

Which of the following statements accurately describes the role of Microtubules (MTs) in a growth cone?

<p>MTs provide a scaffold for the signaling molecules involved in guidance cue reception. (D)</p> Signup and view all the answers

What is the main function of the 'C domain' of Microtubules (MTs) in a growth cone?

<p>To act as a guiding force for the movement of the growth cone (D)</p> Signup and view all the answers

What is the relationship between the 'P domain' of Microtubules (MTs) and F-actin polymerization?

<p>The 'P domain' inhibits F-actin polymerization, slowing the growth cone's movement. (D)</p> Signup and view all the answers

How does the 'T zone' of Microtubules (MTs) contribute to the growth cone's function?

<p>The 'T zone' acts as a connection point between the MTs and the F-actin network, allowing their coordinated activity. (A)</p> Signup and view all the answers

In a growth cone's movement, what role do Microtubules (MTs) and F-actin have relative to each other?

<p>They work in a coordinated manner, with F-actin generating force and MTs providing guidance and signaling. (C)</p> Signup and view all the answers

Which of the following is NOT a direct function of Microtubules (MTs) in a growth cone?

<p>Generating force for the growth cone's movement. (C)</p> Signup and view all the answers

What is the primary function of kinesin 5 in growth cone turning?

<p>Kinesin 5 facilitates MT extension into the P domain by antagonizing dynein. (C)</p> Signup and view all the answers

How do repellent cues influence MT dynamics in the growth cone?

<p>Repellent cues increase MT looping by promoting F-actin retrograde flow. (A)</p> Signup and view all the answers

What is the primary mechanism by which growth cones control MT-actin interactions in response to guidance cues?

<p>Modulating the activity of MAPs, particularly those involved in MT-actin crosslinking. (B)</p> Signup and view all the answers

What is the role of APC in growth cone navigation?

<p>APC binds to a subset of MTs, indicating the future growth direction of the axon. (B)</p> Signup and view all the answers

What is the likely mechanism by which APC contributes to growth cone steering?

<p>APC promotes MT-actin uncoupling, possibly by preventing MT binding to F-actin. (D)</p> Signup and view all the answers

How does the content suggest that motor proteins are targets of guidance cue signaling?

<p>Guidance cues influence the phosphorylation state of motor proteins, modulating their function. (C)</p> Signup and view all the answers

Which of the following best describes the relationship between MTs and actin in the growth cone?

<p>MTs and actin interact dynamically, with the interaction influenced by guidance cues. (C)</p> Signup and view all the answers

What is the significance of the study mentioned in the content regarding APC loss?

<p>APC loss provides evidence for a role of APC in preventing MT binding to F-actin. (B)</p> Signup and view all the answers

Which of the following molecules is NOT explicitly mentioned in the text as being identified in axon guidance assays?

<p>Morphogens (C)</p> Signup and view all the answers

What is the primary function of the growth cone vehicle?

<p>To guide axon growth (B)</p> Signup and view all the answers

Which of the following is NOT a stage of growth cone advance?

<p>Retraction (A)</p> Signup and view all the answers

What is the relationship between a growth cone's motility machinery and environmental factors?

<p>Environmental factors determine the growth cone's direction of movement. (C)</p> Signup and view all the answers

Which of the following statements about attraction and repulsion in axon guidance is TRUE?

<p>Attractive cues can function as ‘stop’ signals, and repulsive cues can function as ‘go’ Signals under certain conditions. (B)</p> Signup and view all the answers

What is the primary focus of the research highlighted in the text?

<p>Investigating the molecular mechanisms of axon guidance. (D)</p> Signup and view all the answers

What is the relationship between F-actin retrograde flow and growth cone motility?

<p>F-actin retrograde flow plays a role in growth cone motility and protrusion. (C)</p> Signup and view all the answers

Where is the Harvard Medical School research group located?

<p>Boston, Massachusetts (C)</p> Signup and view all the answers

What is the likely effect of inhibiting dynein and lIS1 on the movement and growth of a neuronal growth cone?

<p>Reduced ability of MTs to advance into the periphery of the growth cone. (B)</p> Signup and view all the answers

Which of these proteins is directly involved in the coupling of MTs and actin in response to guidance cues?

<p>MAP1B (B)</p> Signup and view all the answers

What is the primary function of lIS1 in regards to microtubule-actin dynamics in the growth cone?

<p>Promoting uncoupling of dynamic MTs from actin retrograde flow. (C)</p> Signup and view all the answers

What is the likely role of GSK3β in the regulation of ClASP function?

<p>GSK3β regulates the binding of ClASP to either the MT plus ends or along the entire MT, potentially affecting its function. (D)</p> Signup and view all the answers

Which of the following is NOT a guidance cue that can activate GSK3β, thereby influencing ClASP function?

<p>Laminin (C)</p> Signup and view all the answers

What is the significance of the MT looping behavior observed in response to guidance cues?

<p>It indicates a potential mechanism for coupling MTs to actin retrograde flow in response to guidance cues. (D)</p> Signup and view all the answers

What is the primary effect of inhibiting myosin II with blebbistatin on MT extension into the growth cone's peripheral domain?

<p>It allows for full recovery of MT extension even in the presence of dynein depletion. (C)</p> Signup and view all the answers

What is the primary function of ClASP as described in the given context?

<p>It potentially drives microtubule-actin coupling and MT loop formation downstream of 'stop' signals. (C)</p> Signup and view all the answers

Flashcards

Growth Cone

A dynamic structure at the tip of a growing axon that guides neuron extension.

Vehicle Function

The aspect of the growth cone that maintains movement and structural integrity.

Navigator Function

Guides the growth cone using environmental signals for directional movement.

Chemotropic Cue

An external chemical signal that directs the growth cone in a gradient.

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Filopodia

Protrusions from the growth cone that extend to sense the environment.

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Axon Guidance

The process by which neurons navigate to their targets during development.

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Cytoskeletal Elements

Structural components that provide the framework for the growth cone.

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Directional Movement

The ability of the growth cone to navigate toward a target based on cues.

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Molecules involved in Axon Guidance

Various factors that assist in directing the growth of axons during development.

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Protrusion

The first stage in growth cone advancement where the cytoskeleton extends forward.

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Engorgement

The second stage in growth cone activity, where the cone swells as it moves.

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Consolidation

The final stage of growth cone movement where it stabilizes its position.

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Attractive Signals

Cues that promote growth cone movement towards them, like netrins.

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Repulsive Signals

Cues that cause growth cones to move away, such as ephrins.

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Cytoskeleton's Role

Supports growth cone movement, allowing it to navigate through stages of motility.

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Microtubules (MTs)

Cylindrical structures that provide support and transport within cells, crucial for growth cone movement.

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F-actin

Filamentous actin, a polymerized form of actin proteins, providing structural support.

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Actin Treadmilling

Dynamic process where actin filaments grow at one end while disassembling at the other.

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Myosin II Contractility

The ability of myosin II proteins to generate force and enable movement or contraction of actin filaments.

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Retrograde Flow

Movement of actin filaments toward the growth cone's cell body, influencing growth dynamics.

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Guidance Cues

Chemical or physical signals that direct the growth cone's path during development.

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Engaged Clutch

A state where the substrate is connected to actin, allowing interactions that aid in growth.

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Cytoskeletal Effectors

Proteins that influence actin dynamics in growth cones.

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Actin Dynamics

The process of actin polymerization and disassembly in cells.

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Rho GTPases

Molecules that regulate actin cytoskeleton for movement directionality.

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GAPs and GEFs

Proteins that activate or inactivate Rho GTPases by changing GTP levels.

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F-actin Assembly

Process of forming filamentous actin at the leading edge of growth cones.

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Arp2/3 Complex

A protein complex that promotes actin filament nucleation.

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Myosin Light Chain Kinase (MLCK)

An enzyme that phosphorylates myosin for muscle contraction and movement.

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ENA/VASP Proteins

Factors involved in actin polymerization and stabilization in growth cones.

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MT-Actin Uncoupling

The separation of microtubules (MT) from actin filaments, enhancing mobility and exploration of the growth cone.

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Kinesin 5

A motor protein that promotes microtubule (MT) extension by moving MTs apart, working against dynein.

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Dynein

Motor protein that generally moves cargo towards the minus end of microtubules, counteracting kinesin's action.

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APC

A +TIP protein that promotes MT-actin uncoupling and interacts with IQGAP1 to guide growth direction.

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MT Exploration

Movement and probing activity of microtubules in the growth cone, influenced by guidance cues.

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MT Looping

A formation where the growing ends of microtubules loop back towards the cell body, influenced by actin interactions.

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MAPs Role

Microtubule-associated proteins (MAPs) regulate microtubule dynamics and interaction with actin in growth cones.

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+TIP Members

+TIP members are proteins that bind to the growing ends of microtubules (MTs).

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lIS1 Function

lIS1 (PAFAH1B1) helps uncouple microtubules from actin in neurons.

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Dynein Role

Dynein is a motor protein that assists in moving microtubules in growth cones.

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GSK3β

GSK3β is a kinase that regulates ClASP's binding to microtubules.

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MAP1B

MAP1B is a scaffold protein that stabilizes microtubules and regulates their dynamics.

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Actin Retrograde Flow

The movement of actin filaments backward in the growth cone, affecting microtubule exploration.

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Microtubule Coupling

The interaction between microtubules and actin filaments that influences growth cone movement.

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Study Notes

Growth Cone Machinery

  • Growth cones are located at the tip of growing axons.
  • They have two key components: a 'vehicle' (for movement) and a 'navigator' (for guidance).
  • The vehicle maintains movement and provides traction.
  • The navigator translates environmental signals into directional movement.

Growth Cone Structure and Function

  • The growth cone has three domains: peripheral (P), central (C), and transition (T).
  • The P domain contains filopodia, lamellipodia-like veils, as well as bundled actin filaments (F-actin bundles).
  • The C domain contains stable microtubules (MTs) and other organelles, vesicles, and central actin bundles.
  • The T zone bridges the P and C domains, including actomyosin contractile structures (actin arcs).

Growth Cone Movement

  • Three stages drive growth cone progression: protrusion, engorgement, and consolidation.
  • Protrusion involves filopodia extending and exploring.
  • Engorgement occurs when microtubules (MTs) further invade.
  • Consolidation happens as actin filaments depolymerize, and the membrane shrinks.
  • F-actin retrograde flow, along with treadmilling, powers growth cone movement.

Growth Cone Navigation

  • Environmental cues guide the growth cone.
  • Adhesive molecules (CAMs, ECM) provide roads.
  • Repellent molecules (slits, ephrins) serve as guard rails.
  • Diffusible chemotropic cues act as road signs.
  • MTs, F-actin, and Rho GTPases underlie navigation.

Growth Cone and Microtubules (MTs)

  • Individual microtubules (MTs) function as guidance sensors in the peripheral (P) domain.
  • Bulk microtubules (MTs) in the central domain steer growth cone advancement.
  • Dynamic instability is a key feature of microtubules (MTs) in growth cones.

Interactions Between Actin and Microtubules

  • Actin retrograde flow and treadmilling drive growth cone motility.
  • Growth cone receptors bind to the substrate, forming a molecular clutch linked to F-actin.
  • F-actin, primarily in filopodia, plays roles in guidance sensing and establishing adhesions.
  • Microtubules (MTs) interact with and are guided by the actin network.
  • The interplay of MTs and actin filaments is crucial for growth cone steering.

Localized Protein Translation

  • Local protein synthesis plays crucial roles in growth cone steering.
  • Guidance cues influence the translation site of proteins, and the localization of certain RNAs.
  • Attractive cues lead to mRNA translation on the leading edge.
  • Repelling cues trigger mRNA translation on the opposing edge.

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