Reexamining actin polymerization in maintaining cadherin mediated cell-cell adhesion

Inhibiting actin polymerization disrupts the cell-cell junction showing that continuous actin polymerization is required for maintaining tissue cohesion. The actin cytoskeleton maintains cell-cell cohesion by converting weak homophilic bonds between the cadherin cell adhesion molecules into strong adhesion. However, the most popular models to explain the role of actin at the junction do not require dynamic actin networks. According to these models, actin polymerization builds contractile actomyosin networks which pull on cadherins and strengthen the mechanosensitive bonds (the contractility model) or the fence around clusters of cadherins which mediate stronger adhesion than single cadherins (the clustering model). Actin polymerization could no doubt achieve these functions but what might be the most direct or evolutionarily primitive function of actin polymerization at junctions? Here I propose an alternative model which emphasizes on the most conceptually direct consequence of continuous actin polymerization: using the energy from ATP hydrolysis by the polymerization motor to drive plasma membrane protrusions; actin polymerization dependent, outwardly directed protrusive forces press the membranes of neighboring cells together in favor of cadherin homophilic binding. In Chapter 2, I show that filopodium-like actin microspikes protrude perpendicularly at the apical junction to deliver cadherins to where cadherins are missing on the neighboring cell, functioning as a repair mechanism for small defects in the otherwise continuous cadherin belt; myosin II contractility, contrary to the popular belief, actually destabilizes junctions. In Chapter 3, I show that interdigitated actin microspikes are engaged with one another through cadherin homophilic bonds at lateral junctions; patches of microspikes appear as micrometer sized cadherin puncta and are a stable form of junction in established epithelia, not only in newly forming tissues; molecular clustering of cadherins persists independently of actin polymerization and do not account for mesoscale cadherin puncta as long believed. Both apical and lateral microspikes depend on actin polymerization factors Arp2/3, EVL, and CRMP-1 and are antagonized by myosin II contractility. Lacking microspikes destabilizes apical and lateral junctions; lacking myosin II ATPase function has no such effect. My works explain why continuous actin polymerization is required for maintaining strong cadherin adhesion while myosin II contractility is dispensable. My works provide a parsimonious explanation for the continuous actin polymerization at junctions by invoking a process (fast, micron-sized membrane protrusion and retraction) that can be achieved by no other cellular apparatus than the dynamic actin cytoskeleton.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Cell and Developmental Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2021

Author dc:creator

• Li, Xiaohe

Contributors dc:contributor

• Brieher, William M
• Belmont, Andrew S
• Chen, Jie
• Leckband, Deborah E

• Actin
• Cadherin
• Cell-cell adhesion
• Cell Junction
• myosin
• clustering
• filopodia
• membrane

Statement dc:rights

• Copyright 2020 Xiaohe Li

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/109358

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/109358