title: SLAIN2 links microtubule plus end-tracking proteins and controls microtubule growth in interphase.
abstract: The ends of growing microtubules (MTs) accumulate a set of diverse factors known as MT plus end-tracking proteins (+TIPs), which control microtubule dynamics and organization. In this paper, we identify SLAIN2 as a key component of +TIP interaction networks. We showed that the C-terminal part of SLAIN2 bound to end-binding proteins (EBs), cytoplasmic linker proteins (CLIPs), and CLIP-associated proteins and characterized in detail the interaction of SLAIN2 with EB1 and CLIP-170. Furthermore, we found that the N-terminal part of SLAIN2 interacted with ch-TOG, the mammalian homologue of the MT polymerase XMAP215. Through its multiple interactions, SLAIN2 enhanced ch-TOG accumulation at MT plus ends and, as a consequence, strongly stimulated processive MT polymerization in interphase cells. Depletion or disruption of the SLAIN2-ch-TOG complex led to disorganization of the radial MT array. During mitosis, SLAIN2 became highly phosphorylated, and its interaction with EBs and ch-TOG was inhibited. Our study provides new insights into the molecular mechanisms underlying cell cycle-specific regulation of MT polymerization and the organization of the MT network.
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, 3000 CA Rotterdam, Netherlands.
authors.forename: Babet
authors.initials: B
authors.lastname: van der Vaart
authors.forename: Cristina
authors.initials: C
authors.lastname: Manatschal
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Vincent
authors.initials: V
authors.lastname: Olieric
authors.forename: Susana Montenegro
authors.initials: SM
authors.lastname: Gouveia
authors.forename: Sasa
authors.initials: S
authors.lastname: Bjelic
authors.forename: Jeroen
authors.initials: J
authors.lastname: Demmers
authors.forename: Ivan
authors.initials: I
authors.lastname: Vorobjev
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D007399:Interphase / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C405804:EB1 microtubule binding proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C510771:SLAIN1 protein, human; C561112:SLAIN2 protein, human; C076744:cytoplasmic linker protein 170