Binh-An Truong Quang1, Madhav Mani2, Olga Markova1, Thomas Lecuit1, Pierre-François Lenne3. 1. Developmental Biology Institute of Marseilles, UMR 7288 CNRS, Aix-Marseille Université, 13288 Marseille Cedex 9, France. 2. Kavli Institute of Theoretical Physics, Santa Barbara, CA 93101, USA; University of California, Department of Physics, Santa Barbara, CA 93101, USA. 3. Developmental Biology Institute of Marseilles, UMR 7288 CNRS, Aix-Marseille Université, 13288 Marseille Cedex 9, France. Electronic address: pierre-francois.lenne@univ-amu.fr.
Abstract
BACKGROUND: E-cadherin plays a pivotal role in tissue morphogenesis by forming clusters that support intercellular adhesion and transmit tension. What controls E-cadherin mesoscopic organization in clusters is unclear. RESULTS: We use 3D superresolution quantitative microscopy in Drosophila embryos to characterize the size distribution of E-cadherin nanometric clusters. The cluster size follows power-law distributions over three orders of magnitude with exponential decay at large cluster sizes. By exploring the predictions of a general theoretical framework including cluster fusion and fission events and recycling of E-cadherin, we identify two distinct active mechanisms setting the cluster-size distribution. Dynamin-dependent endocytosis targets large clusters only, thereby imposing a cutoff size. Moreover, interactions between E-cadherin clusters and actin filaments control the fission in a size-dependent manner. CONCLUSIONS: E-cadherin clustering depends on key cortical regulators, which provide tunable and local control over E-cadherin organization. Our data provide the foundation for a quantitative understanding of how E-cadherin distribution affects adhesion and might regulate force transmission in vivo.
BACKGROUND:E-cadherin plays a pivotal role in tissue morphogenesis by forming clusters that support intercellular adhesion and transmit tension. What controls E-cadherin mesoscopic organization in clusters is unclear. RESULTS: We use 3D superresolution quantitative microscopy in Drosophila embryos to characterize the size distribution of E-cadherin nanometric clusters. The cluster size follows power-law distributions over three orders of magnitude with exponential decay at large cluster sizes. By exploring the predictions of a general theoretical framework including cluster fusion and fission events and recycling of E-cadherin, we identify two distinct active mechanisms setting the cluster-size distribution. Dynamin-dependent endocytosis targets large clusters only, thereby imposing a cutoff size. Moreover, interactions between E-cadherin clusters and actin filaments control the fission in a size-dependent manner. CONCLUSIONS:E-cadherin clustering depends on key cortical regulators, which provide tunable and local control over E-cadherin organization. Our data provide the foundation for a quantitative understanding of how E-cadherin distribution affects adhesion and might regulate force transmission in vivo.
Authors: Robert J Huebner; Abdul Naseer Malmi-Kakkada; Sena Sarıkaya; Shinuo Weng; D Thirumalai; John B Wallingford Journal: Elife Date: 2021-05-25 Impact factor: 8.140