History-Dependent Catastrophes Regulate Axonal Microtubule Behavior

T (Tatiana) Stepanova, Ihor Smal, J van Haren, Umut Akinci Çorbacioğlu, Zhe Liu, M (Marja) Miedema, RWA (Ronald) Limpens, MA van Ham, Michael Reijden, Raymond Poot, Frank Grosveld, M Mommaas, Erik Meijering, Niels Galjart

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

In Chinese hamster ovary cells, microtubules originate at the microtubule organizing center (MTOC) and grow persistently toward the cell edge, where they undergo catastrophe [1]. In axons, microtubule dynamics must be regulated differently because microtubules grow parallel to the plasma membrane and there is no MTOC. GFP-tagged microtubule plus end tracking proteins (+TIPs) mark the ends of growing neuronal microtubules [2]. Their fluorescent "comet-like" pattern reflects turnover of +TIP binding sites [3, 4]. Using GFP-tagged +TIPs and fluorescence-based segmentation and tracking tools, we show that axonal microtubules grow with a constant average velocity and that they undergo catastrophes at random positions, yet in a programmed fashion. Using protein depletion approaches, we find that the +TIPs CLIP-115 and CLIP-170 affect average microtubule growth rate and growth distance in neurons but not the duration of a microtubule growth event. In N1E-115 neuroblastoma cells, we find that EB1, the core +TIP [5], regulates microtubule growth rate, growth distance, and duration, consistent with in vitro data [6]. Combined, our data suggest that CLIPs influence the axonal microtubule/tubulin ratio, whereas EB1 stimulates microtubule growth and structural transitions at microtubule ends, thereby regulating microtubule catastrophes and the turnover of +TIP binding sites.
Original languageEnglish
Pages (from-to)1023-1028
Number of pages6
JournalCurrent Biology
Volume20
Issue number11
DOIs
Publication statusPublished - 2010

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