Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes.
The transition of microtubules (MTs) from an assembled to a disassembled state plays an essential role in several cellular functions. While MT dynamics are often linked to those of actin filaments, little is known about whether intermediate filaments (IFs) have an influence on MT dynamics. We show here that plectin 1c (P1c), one of the multiple isoforms of the IF-associated cytolinker protein plectin, acts as an MT destabilizer. We found that MTs in P1c-deficient (P1c(-/-)) keratinocytes are more resistant toward nocodazole-induced disassembly and display increased acetylation. In addition, live imaging of MTs in P1c(-/-), as well as in plectin-null, cells revealed decreased MT dynamics. Increased MT stability due to P1c deficiency led to changes in cell shape, increased velocity but loss of directionality of migration, smaller-sized focal adhesions, higher glucose uptake, and mitotic spindle aberrations combined with reduced growth rates of cells. On the basis of ex vivo and in vitro experimental approaches, we suggest a mechanism for MT destabilization in which isoform-specific binding of P1c to MTs antagonizes the MT-stabilizing and assembly-promoting function of MT-associated proteins through an inhibitory function exerted by plectin's SH3 domain. Our results open new perspectives on cytolinker-coordinated IF-MT interaction and its physiological significance.
Max F. Perutz Laboratories, Department of Biochemistry and Cell Biology, University of Vienna, A-1030 Vienna, Austria.
Rocio G
RG
Valencia
Gernot
G
Walko
Lubomir
L
Janda
Jirka
J
Novacek
Eva
E
Mihailovska
Siegfried
S
Reipert
Kerstin
K
Andrä-Marobela
Gerhard
G
Wiche
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D022001:Focal Adhesions / Q000235:genetics; D007382:Intermediate Filaments / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D051179:Plakins / Q000378:metabolism; D051190:Plectin / Q000378:metabolism*; D008941:Spindle Apparatus; D050257:Tubulin Modulators / Q000494:pharmacology
D051179:Plakins; C495333:Plec protein, mouse; D051190:Plectin; D050257:Tubulin Modulators; D015739:Nocodazole