Laminin-based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5alpha/beta.
LL5beta has been identified as a microtubule-anchoring factor that attaches EB1/CLIP-associating protein (CLASP)-bound microtubule plus ends to the cell cortex. In this study, we show that LL5beta and its homologue LL5alpha (LL5s) colocalize with autocrine laminin-5 and its receptors, integrins alpha3beta1 and alpha6beta4, at the basal side of fully polarized epithelial sheets. Depletion of both laminin receptor integrins abolishes the cortical localization of LL5s, whereas LL5 depletion reduces the amount of integrin alpha3 at the basal cell cortex. Activation of integrin alpha3 is sufficient to initiate LL5 accumulation at the cell cortex. LL5s form a complex with the cytoplasmic tails of these integrins, but their interaction might be indirect. Analysis of the three-dimensional distribution of microtubule growth by visualizing EB1-GFP in epithelial sheets in combination with RNA interference reveals that LL5s are required to maintain the density of growing microtubules selectively at the basal cortex. These findings reveal that signaling from laminin-integrin associations attaches microtubule plus ends to the epithelial basal cell cortex.
KAN Research Institute, Inc., Chuo-ku, Kobe 650-0047, Japan.
Azusa
A
Hotta
Tomomi
T
Kawakatsu
Tomoya
T
Nakatani
Toshitaka
T
Sato
Chiyuki
C
Matsui
Taiko
T
Sukezane
Tsuyoshi
T
Akagi
Tomoko
T
Hamaji
Ilya
I
Grigoriev
Anna
A
Akhmanova
Yoshimi
Y
Takai
Yuko
Y
Mimori-Kiyosue
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism
C497850:CLASP1 protein, human; D002352:Carrier Proteins; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D039503:Integrin alpha6; D039161:Integrin alpha6beta4; D047908:Intracellular Signaling Peptides and Proteins; C400567:LAMC2 protein, human; D007797:Laminin; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C487973:PHLDB1 protein, human; C471180:PHLDB2 protein, human; D034741:RNA, Small Interfering; D017474:Receptors, Laminin