presentation

Chapter 1: Introduction

  • Key Points of Trafficking Integrins

    • Importance of Trafficking

      • Regulates integrins at the cell surface

      • Continuous internalisation and recycling control positioning and availability for adhesion complexes.

    • Internalisation and Adhesion Complexes

      • Critical for disassembly of adhesion complexes, enabling cell movement.

      • Recycled integrins are incorporated into newly formed adhesion complexes, affecting their formation.

    • Trafficking and RGTPase Activation

      • Influences protrusion formation in cells.

    • References for Additional Reading

      • Two key reviews recommended for deeper insights.

    • Focal Adhesion Kinase (FAC)

      • Knockout impairs cell motility

      • Slow turnover of adhesion complexes; associated with protease calpain.

      • Recruitment of microtubules regulates integrin endocytosis.

Chapter 2: Endocytosis of Integrins

  • Endocytic Trafficking Overview

    • Proteins are produced in the ER, processed in the Golgi, and trafficked to the cell surface.

    • Integrins internalised from plasma membrane into endosomes, trafficking through the endolysosomal system leading to lysosome destinations for degradation.

    • Early Endosomes and Recycling

      • Cargo sorting occurs in early endosomes before recycling back to plasma membrane.

      • Importantly regulated paths: Clathrin-dependent and independent endocytosis.

      • RAB5 plays a vital role in early sorting and RAB21 directly interacts with alpha1beta1 integrins, influencing internalisation.

  • Routes of Endocytosis

    • Clathrin-mediated is the most understood, involving dynamin for vesicle internalisation.

    • Also includes clathrin-independent carriers and caveolae.

Chapter 3: Polarity of Integrins

  • Integrin Internalisation Routes

    • Various pathways, including direct internalisation from nascent adhesions and mature focal complexes.

    • Roles of Focal Adhesion Kinase (FAC)

      • Critical for microtubule targeting to adhesion sites, facilitating internalisation via DAB2 and dynamin.

    • Regulatory Interactions

      • RAB 5 and other proteins can polarize to adhesion sites to assist clathrin-mediated endocytosis.

Chapter 4: Active Integrins

  • Active Integrins in Endosomes

    • Active state of integrins maintained in endosomes by FAC involvement.

    • Essential for new adhesion complex assembly at the leading edge of migrating cells.

  • Recycling Mechanisms

    • RAB4 and PKD-dependent recycling towards the leading edge.

    • Experimental Findings

      • Beta3 integrins can internalise via macropinocytosis, returning to plasma membrane as active components.

Chapter 5: Integrins on Endosomes

  • Role of FAC

    • Maintains active integrins for proper recycling back to membrane for new adhesion complex formation.

    • Inhibition of FAC disrupts this process, leading to ineffective adhesion development.

  • Impact on Signalling

    • Integrins can interact with signalling pathways important for |cancer progression including anoikis suppression.

Chapter 6: Spiky Looking Protrusions

  • 3D Migration Context

    • Protrusions in 3D environments differ from those in 2D, necessitating cells to adapt migration methods through various integrin signalling.

    • Actin Dynamics

      • Rho GTPases regulate actin polymerization.

    • Experimental Methods

      • Magnetic particles used to manipulate endosomal positions, aiding understanding of protrusion formation.

Chapter 7: Conclusion

  • Summary of Concepts

    • Constitutive internalisation and recycling of integrins is vital for cellular processes.

    • Varying routes of trafficking depend on specific interactions and cellular contexts.

    • Integrin internalisation critical for controlling disassembly of adhesion complexes and influencing cell motility through Rho GTPase activity.