New insights into an old organelle: meeting report on biology of cilia and flagella.

The rising interest of the scientific community in cilia biology was evident from the fact that registration for the third FASEB conference on 'The Biology of Cilia and Flagella' closed out before the early bird deadline. Cilia and flagella are organelles of profound medical importance; defects in their structure or function result in a plethora of human diseases called ciliopathies. 240 clinicians and basic scientists from around the world gathered from 23 June 2013 to 28 June 2013 at Sheraton at the Falls, Niagara Falls, NY to present and discuss their research on this intensely studied subcellular structure. The meeting was organized by Gregory Pazour (University of Massachusetts Medical School), Bradley Yoder (University of Alabama-Birmingham), and Maureen Barr (Rutgers University) and was sponsored by the Federation of American Societies for Experimental Biology (FASEB). Here, we report highlights, points of discussion, and emerging themes from this exciting meeting.

Tubulin perturbation leads to unexpected cell wall modifications and affects stomatal behaviour in Populus.

Cortical microtubules are integral to plant morphogenesis, cell wall synthesis, and stomatal behaviour, presumably by governing cellulose microfibril orientation. Genetic manipulation of tubulins often leads to abnormal plant development, making it difficult to probe additional roles of cortical microtubules in cell wall biogenesis. Here, it is shown that expressing post-translational C-terminal modification mimics of α-tubulin altered cell wall characteristics and guard cell dynamics in transgenic Populus tremula x alba that otherwise appear normal. 35S promoter-driven transgene expression was high in leaves but unusually low in xylem, suggesting high levels of tubulin transgene expression were not tolerated in wood-forming tissues during regeneration of transformants. Cellulose, hemicellulose, and lignin contents were unaffected in transgenic wood, but expression of cell wall-modifying enzymes, and extractability of lignin-bound pectin and xylan polysaccharides were increased in developing xylem. The results suggest that pectin and xylan polysaccharides deposited early during cell wall biogenesis are more sensitive to subtle tubulin perturbation than cellulose and matrix polysaccharides deposited later. Tubulin perturbation also affected guard cell behaviour, delaying drought-induced stomatal closure as well as light-induced stomatal opening in leaves. Pectins have been shown to confer cell wall flexibility critical for reversible stomatal movement, and results presented here are consistent with microtubule involvement in this process. Taken together, the data show the value of growth-compatible tubulin perturbations for discerning microtubule functions, and add to the growing body of evidence for microtubule involvement in non-cellulosic polysaccharide assembly during cell wall biogenesis.

Tubulin Post-translational Modifications: Potential Therapeutic Approaches to Heart Failure.

In recent decades, advancing insights into the mechanisms of cardiac dysfunction have focused on the involvement of microtubule network. A variety of tubulin post-translational modifications have been discovered to fine-tune the microtubules' properties and functions. Given the limits of therapies based on conserved structures of the skeleton, targeting tubulin modifications appears to be a potentially promising therapeutic strategy. Here we review the current understanding of tubulin post-translational modifications in regulating microtubule functions in the cardiac system. We also discussed how altered modifications may lead to a range of cardiac dysfunctions, many of which are linked to heart failure.

Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini.

Most adult neurons and glia originate from radial glial progenitors (RGs), a type of stem cell typically extending from the apical to the basal side of the developing cortex. Precise regulation of the choice between RG self-renewal and differentiation is critical for normal development, but the mechanisms underlying this transition remain elusive. We show that the non-canonical tubulin Tuba8, transiently expressed in cortical progenitors, drives differentiation of RGs into apical intermediate progenitors, a more restricted progenitor type lacking attachment to the basal lamina. This effect depends on the unique C-terminal sequence of Tuba8 that antagonizes tubulin tyrosination and Δ2 cleavage, two post-translational modifications (PTMs) essential for RG fiber maintenance and the switch between direct and indirect neurogenesis and ultimately distinct neuronal lineage outcomes. Our work uncovers an instructive role of a developmentally regulated tubulin isotype in progenitor differentiation and provides new insights into biological functions of the cellular tubulin PTM "code."

Effect of Tubastatin A on the Functional Recovery of Cauda Equina Injury in Rats.

OBJECTIVE: To explore the effect of the inhibitor of histone deacetylase (6HDAC6), tubastatin A, on the functional recovery of injured central branch of dorsal root ganglia (cauda equina). METHODS: A total of 30 Sprague-Dawley rats (n = 10 for each group) were divided randomly into sham operation (sham group), cauda equina compression control (CEC control group), and cauda equina compression plus tubastatin A treatment (tubastatin A group). The tail-flick test was performed to detect the sense of pain and warmth as well as motor function. Immunoblotting/immunofluorescence experiments, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and hematoxylin-eosin staining were performed to detect the amount of HDAC6 in dorsal root ganglion (DRG) neurons, degree of apoptosis in DRG neurons, and degree of cauda equina injury, respectively. RESULTS: The ratio of apoptotic cells in the CEC control group was greater than that in the sham group, whereas it decreased in the tubastatin A group. Hematoxylin-eosin staining revealed that the fibers of cauda equina in the tubastatin A group were more compact compared with those in the CEC control group. The expression of HDAC6 was not different between the sham and CEC control groups, whereas it decreased significantly in the tubastatin A group. Tubastatin A administration shortened tail-flick latency on the seventh day after operation compared with the CEC control group. CONCLUSIONS: Tubastatin A significantly decreased the expression of HDAC6 in DRG neurons with injured cauda equina, inhibited the apoptosis of neural cells and axonal demyelinating changes in cauda equina, and partially promoted the recovery of neural function.