GAS2-like proteins mediate communication between microtubules and actin through interactions with end-binding proteins.
Crosstalk between the microtubule (MT) and actin cytoskeletons is fundamental to many cellular processes including cell polarisation and cell motility. Previous work has shown that members of the growth-arrest-specific 2 (GAS2) family mediate the crosstalk between filamentous actin (F-actin) and MTs, but the molecular basis of this process remained unclear. By using fluorescence microscopy, we demonstrate that three members of this family, GAS2-like 1, GAS2-like 2 and GAS2-like 3 (G2L1, G2L2 and G2L3, also known as GAS2L1, GAS2L2 and GAS2L3, respectively) are differentially involved in mediating the crosstalk between F-actin and MTs. Although all localise to actin and MTs, only the exogenous expression of G2L1 and G2L2 influenced MT stability, dynamics and guidance along actin stress fibres. Biochemical analysis and live-cell imaging revealed that their functions are largely due to the association of these proteins with MT plus-end-binding proteins that bind to SxIP or SxLP motifs located at G2L C-termini. Our findings lead to a model in which end-binding (EB) proteins play a key role in mediating actin-MT crosstalk.
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Matthew J
MJ
Stroud
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Alicja
A
Nazgiewicz
Manchester Institute of Biotechnology, Faculty of Life Sciences, 131 Princess Street, Manchester M1 7DN, UK.
Edward A
EA
McKenzie
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Yisu
Y
Wang
Laboratory of Biomolecular Research, OFLC 106, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland.
Richard A
RA
Kammerer
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK christoph.ballestrem@manchester.ac.uk.
Christoph
C
Ballestrem
D000199:Actins / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011485:Protein Binding; D021382:Protein Sorting Signals; D021381:Protein Transport; D022502:Stress Fibers / Q000378:metabolism*
D000199:Actins; C490934:GAS2L1 protein, human; C000594829:GAS2L2 protein, human; C500985:MAPRE1 protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D021382:Protein Sorting Signals
Actin; End-binding protein; GAS2 family; GAS2-like 1; GAS2-like 2; GAS2-like 3; MT-tip localising signal; Microtubule; MtLS