Kinetics of microtubule catastrophe assessed by probabilistic analysis

Abstract

Microtubules are cytoskeletal filaments whose self-assembly occurs by abrupt switching between states of roughly constant growth and shrinkage, a process known as dynamic instability. Understanding the mechanism of dynamic instability offers potential for controlling microtubule-dependent cellular processes such as nerve growth and mitosis. The growth to shrinkage transitions (catastrophes) and the reverse transitions (rescues) that characterize microtubule dynamic instability have been assumed to be random events with first-order kinetics. By direct observation of individual microtubules in vitro and probabilistic analysis of their distribution of growth times, we found that while the slower growing and biologically inactive (minus) ends obeyed first-order catastrophe kinetics, the faster growing and biologically active (plus) ends did not. The non-first-order kinetics at plus ends imply that growing microtubule plus ends have an effective frequency of catastrophe that depends on how long the microtubules have been growing. This frequency is low initially but then rises asymptotically to a limiting value. Our results also suggest that an additional parameter, beyond the four parameters typically used to describe dynamic instability, is needed to account for the observed behavior and that changing this parameter can significantly affect the distribution of microtubule lengths at steady state.

Microtubule catastrophe from protofilament dynamics

“…It has been shown experimentally, first by Odde et al [24] and more recently by Stepanova et al [25] and Gardner et al [26] that microtubule catastrophes have a certain historydependence, i.e., the probability for a microtubule to undergo catastrophe appears to depend on how long its has been growing. Based on these observations, it was suggested that catastrophe is a multi-step process, which requires a certain number of events to occur for its materialization.…”

Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability

“…Analysis of filament lifetimes by using catastrophe time was conducted in analogy to Gardner et al (19). According to Odde et al (43,44), they can be described by using a gamma distribution where the predicted number of catastrophes at a given time t are dFnðtÞ dt = r n t n-1 e -rt ΓðnÞ dFnðtÞ dt = r n t n−1 e −rt ΓðnÞ ðprobability density functionÞ.…”

Microtubule assembly dynamics: new insights at the nanoscale

“…The frequency at which a growing MT tip switches to a shortening state is called the "catastrophe" frequency, while "rescue" frequency is the frequency at which a shortening MT tip switches into a growing state [2]. Numerous studies using light microscopy have quantitatively characterized this behavior both in vitro and in vivo [3][4][5].…”