Septins mediate a microtubule-actin crosstalk that enables actin growth on microtubules

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 119; no. 50; p. e2202803119
• Main Authors: Nakos, Konstantinos, Alam, Md Noor A, Radler, Megan R, Kesisova, Ilona A, Yang, Changsong, Okletey, Joshua, Tomasso, Meagan R, Padrick, Shae B, Svitkina, Tatyana M, Spiliotis, Elias T
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13-12-2022
• Subjects: Actin; Actins; Biological Sciences; Cell division; Cell migration; Cones; Crosstalk; Cytoskeleton; Electron microscopy; Filaments; Growth cones; Intermediate filaments; Lattices; Microtubules; Morphogenesis; Platinum; Polymerization; Septin; Septins; actin–microtubule crosstalk; actin; microtubules; growth cones; septins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2202803119

Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. Microtubule-actin crosstalk is poorly understood and largely regarded as the capture and regulation of microtubules by actin. Septins are filamentous guanosine-5'-triphosphate (GTP) binding proteins, which comprise the fourth component of the cytoskeleton along microtubules, actin, and intermediate filaments. Here, we report that septins mediate microtubule-actin crosstalk by coupling actin polymerization to microtubule lattices. Superresolution and platinum replica electron microscopy (PREM) show that septins localize to overlapping microtubules and actin filaments in the growth cones of neurons and non-neuronal cells. We demonstrate that recombinant septin complexes directly crosslink microtubules and actin filaments into hybrid bundles. In vitro reconstitution assays reveal that microtubule-bound septins capture and align stable actin filaments with microtubules. Strikingly, septins enable the capture and polymerization of growing actin filaments on microtubule lattices. In neuronal growth cones, septins are required for the maintenance of the peripheral actin network that fans out from microtubules. These findings show that septins directly mediate microtubule interactions with actin filaments, and reveal a mechanism of microtubule-templated actin growth with broader significance for the self-organization of the cytoskeleton and cellular morphogenesis.