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Updated: Aug 13, 2025

In Vitro Polymerization of F-actin on Early Endosomes
Published on: August 28, 2017
Vesicle-Associated Actin Assembly by Formins Promotes TGFβ-Induced ANGPTL4 Trafficking, Secretion and Cell Invasion
Dennis Frank1, Christel Jessica Moussi1,2, Svenja Ulferts1
1Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, 79104, Freiburg, Germany.
Abstract:
Vesicle trafficking has emerged as an important process driving tumor progression through various mechanisms. Transforming growth factor beta (TGFβ)-mediated secretion of Angiopoietin-like 4 (ANGPTL4) is important for cancer development. Here, Formin-like 2 (FMNL2) is identified to be necessary for ANGPTL4 trafficking and secretion in response to TGFβ. Protein kinase C (PKC)-dependent phosphorylation of FMNL2 downstream of TGFβ stimulation is required for cancer cell invasion as well as ANGPTL4 vesicle trafficking and secretion. Moreover, using super resolution microscopy, ANGPTL4 trafficking is actin-dependent with FMNL2 directly polymerizing actin at ANGPTL4-containing vesicles, which are associated with Rab8a and myosin Vb. This work uncovers a formin-controlled mechanism that transiently polymerizes actin directly at intracellular vesicles to facilitate their mobility. This mechanism may be important for the regulation of cancer cell metastasis and tumor progression.
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