Molecular Pathway of Microtubule Organization at the Golgi Apparatus.
The Golgi apparatus controls the formation of non-centrosomal microtubule arrays important for Golgi organization, polarized transport, cell motility, and cell differentiation. Here, we show that CAMSAP2 stabilizes and attaches microtubule minus ends to the Golgi through a complex of AKAP450 and myomegalin. CLASPs stabilize CAMSAP2-decorated microtubules but are not required for their Golgi tethering. AKAP450 is also essential for Golgi microtubule nucleation, and myomegalin and CDK5RAP2 but not CAMSAP2 contribute to this function. In the absence of centrosomes, AKAP450- and CAMSAP2-dependent pathways of microtubule minus-end organization become dominant, and the presence of at least one of them is needed to maintain microtubule density. Strikingly, a compact Golgi can be assembled in the absence of both centrosomal and Golgi microtubules. However, CAMSAP2- and AKAP450-dependent Golgi microtubules facilitate Golgi reorientation and cell invasion in a 3D matrix. We propose that Golgi-anchored microtubules are important for polarized cell movement but not for coalescence of Golgi membranes.
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Jingchao
J
Wu
Department of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Cecilia
C
de Heus
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Qingyang
Q
Liu
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Benjamin P
BP
Bouchet
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Ivar
I
Noordstra
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Kai
K
Jiang
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Shasha
S
Hua
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Maud
M
Martin
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Chao
C
Yang
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Ilya
I
Grigoriev
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Eugene A
EA
Katrukha
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, The Netherlands Proteomics Centre, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
A F Maarten
AFM
Altelaar
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Casper C
CC
Hoogenraad
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Robert Z
RZ
Qi
Department of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Judith
J
Klumperman
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. Electronic address: a.akhmanova@uu.nl.
Anna
A
Akhmanova
D054758:A Kinase Anchor Proteins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D002502:Centrioles / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007425:Intracellular Membranes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; C000608274:Camsap3 protein, human; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D011743:Pyrimidines; D013450:Sulfones; D014404:Tubulin; C000599097:centrinone