Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation

Neurite growth requires two guanine nucleotide-binding protein polymers of tubulins and septins. However, whether and how those cytoskeletal systems are coordinated was unknown. Here we show that the acute knockdown or knockout of the pivotal septin subunit SEPT7 from cerebrocortical neurons impairs their interhemispheric and cerebrospinal axon projections and dendritogenesis in perinatal mice, when the microtubules are severely hyperacetylated. The resulting hyperstabilization and growth retardation of microtubules are demonstrated in vitro. The phenotypic similarity between SEPT7 depletion and the pharmacological inhibition of α-tubulin deacetylase HDAC6 reveals that HDAC6 requires SEPT7 not for its enzymatic activity, but to associate with acetylated α-tubulin. These and other findings indicate that septins provide a physical scaffold for HDAC6 to achieve efficient microtubule deacetylation, thereby negatively regulating microtubule stability to an optimal level for neuritogenesis. Our findings shed light on the mechanisms underlying the HDAC6-mediated coupling of the two ubiquitous cytoskeletal systems during neural development

Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents

The effect of hot-pack warming on the deep body temperature -for the development of a nursing care instrument to induce sleep-

A hot-pack made of a dense polymer and covered with a cloth was manufactured as a warming instrument. This hot-pack can be readily warmed in a microwave oven. The present study was performed to examine the effects of warming the lower limbs using this hot-pack on the temperature and blood flow at various sites including the toe, mid-thigh, chest, and forehead. The results were as follows: 1. Hot-pack warming raised the deep body temperature. 2. Lower limb warming by the hot-pack increased the blood flow, by which the increase in temperature spread to the central part of the body. 3. The deep body temperature fell following the removal of the hot-pack, and, in addition, by sweating. It is suggested that hot-pack warming might be useful for inducing sleep in elderly people

The effect of hot-pack warming on the skin temperature of the elderly

A hot-pack made of a dense polymer and warmed in a microwave oven can be used as a warming instrument. This study was performed to examine the effects of a hot-pack, which was used to warm the lower limbs, on the skin surface temperature of elderly people living in a nursing home. The results demonstrated that hot-pack warming is useful to increase the skin surface temperature of elderly people and to maintain a hyperthermic effect. This method of hot-pack warming can also be used as thermal therapy in elderly people living in nursing homes

Fast thermal denaturation of the hyperthermophilic protein, ST1625 product

Protein folding and misfolding (1), Poster Session, Abstract, Meeting Program of EABS & BSJ 200