The Multipurpose 15-Protofilament Microtubules in C. elegans Have Specific Roles in Mechanosensation

Abstract

Summary Because microtubules perform many essential functions in neurons, delineating unique roles attributable to these organelles presents a formidable challenge. Microtubules endow neurons with shape and structure and are required for developmental processes including neurite outgrowth [1], intracellular transport [2], and synaptic formation and plasticity [3, 4]; microtubules in sensory neurons may be required for the above processes in addition to a specific sensory function. In Caenorhabditis elegans six touch receptor neurons (TRNs) sense gentle touch [5] and uniquely contain 15-protofilament microtubules [6]. Disruption of these microtubules by loss of either the MEC-7 β-tubulin [7] or MEC-12 a-tubulin [8] or by growth in 1 mM colchicine causes touch insensitivity [5, 6], altered distribution of the touch transduction channel, and a general reduction in protein levels. We show that the effect on touch sensitivity can be separated from the others; microtubule depolymerization in mature TRNs causes touch insensitivity but does not result in protein distribution and production defects. In addition, the mec-12(e1605) mutation selectively causes touch insensitivity without affecting microtubule formation and other cellular processes. Touching e1605 animals produces a reduced mechanoreceptor current that inactivates more rapidly than in wild type, suggesting a specific role of the microtubules in mechanotransduction.

Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons

“…Disrupting the mechanosensory channel components abolished the evoked touch current in the neurons, and a mutation in the α-tubulin MEC-12, e1605, also significantly reduced this current (15,28). Overactivation of the hyperpolarizing potassium channel SLO-1 impaired neuronal excitability and triggered progressive neuronal defects.…”

Specific α- and β-Tubulin Isotypes Optimize the Functions of Sensory Cilia inCaenorhabditis elegans

“…In particular, tubulins can play an important role in linking channel proteins with the cytoskeleton (Li et al 2006a;Bounoutas et al 2009). Many of the neurons in which we observed sensory defects are thought to sense mechanosensory stimuli, including the nose-touch neurons OLQ, ASH, and FLP (Kaplan and Horvitz 1993) (Left) For each genotype, the the entire set of rays is shown.…”

“…These nonciliated cells harbor unusual 15-filament microtubules composed of dimers of the a-tubulin MEC-12 and the b-tubulin MEC-7. The loss of mec-7 or mec-12, the expression of which is largely restricted to these cells, results in the conversion of 15-filament microtubules to the standard 11-microfilament variety and a commensurate loss of light-touch response (Savage et al 1989;Fukushige et al 1999;Bounoutas et al 2009). Thus experimental support exists for both of these opposing views, and it seems likely that the role of specific tubulin isoforms in regulating microtubule structure and function differs according to cell and organelle type.…”

Spatio-temporal dynamics of β-tubulin isotypes during the development of the sensory auditory organ in rat

“…This structural organization could be lost by the inhibition of mec-12 (α-tubulin) and mec-7 (β-tubulin). The mutational studies indicated clearly that this specific heterodimer was essential in the formation of 15-protofilament microtubules and that this structure was fundamental for the touch sense (Savage et al 1989;Fukushige et al 1999;Bounoutas et al 2009;Wade 2009). …”