Cytoskeletal connections: building strong cells in new ways

Cell and tissue integrity requires the coordination of actin and microtubules and the linkage of these cytoskeletal elements to cell junctions. New findings reveal that the cytoskeletal linker protein Short stop works with EB1 and APC1 to help carry out this function.     

Initial results and long-term clinical follow-up of an amorphous hydrogenated silicon-carbide-coated stent in daily practice

The hemocompatibility and biocompatibility of a stent are determined by the physical and electrochemical properties of the stent surface. The aim of this study was to determine the feasibility, safety and efficacy of implantation of a stent coated with silicon carbide. Baseline characteristics were collected prospectively. The occurrence of cardiac adverse events and the angina score were assessed at clinical follow-up. A total of 193 Tensum stents were implanted in 174 patients. In hospital, one patient experienced stent thrombosis and in 6% of the patients a creatinine kinase elevation to 240 U/l or more occurred. Long-term follow-up was performed in 172 patients, with a mean follow-up of 454 +/- 181 days. Ninety-seven per cent were still alive, 15% had undergone target-vessel revascularization, and 2% had angiographic restenosis and were treated with medication only. Seventy-one per cent of the patients were free of anginal complaints, and 20% had anginal complaints in Canadian Cardiac Society class I or II. The Tensum coronary stent showed to be a safe and efficacious device in this study, with a high primary success rate and favorable long-term clinical followup.     

Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout of ACSL1 (Acsl1^T−/−) have impaired cardiac fatty acid oxidation and rely on glucose for ATP production. Because ACSL1 exhibited a strong substrate preference for linoleate, we investigated the composition of heart phospholipids. Acsl1^T−/− hearts contained 83% less tetralinoleoyl-cardiolipin (CL), the major form present in control hearts. A stable knockdown of ACSL1 in H9c2 rat cardiomyocytes resulted in low incorporation of linoleate into CL and in diminished incorporation of palmitate and oleate into other phospholipids. Overexpression of ACSL1 in H9c2 and HEK-293 cells increased incorporation of linoleate into CL and other phospholipids. To determine whether increasing the content of linoleate in CL would improve mitochondrial respiratory function in Acsl1^T−/− hearts, control and Acsl1^T−/− mice were fed a high-linoleate diet; this diet normalized the amount of tetralinoleoyl-CL but did not improve respiratory function. Thus, ACSL1 is required for the normal composition of several phospholipid species in heart. Although ACSL1 determines the acyl-chain composition of heart CL, a high tetralinoleoyl-CL content may not be required for normal function.     

Abelson kinase regulates epithelial morphogenesis in Drosophila.

Activation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and alpha-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.