The primary cilium as the cell's antenna: signaling at a sensory organelle.

Almost every vertebrate cell has a specialized cell surface projection called a primary cilium. Although these structures were first described more than a century ago, the full scope of their functions remains poorly understood. Here, we review emerging evidence that in addition to their well-established roles in sight, smell, and mechanosensation, primary cilia are key participants in intercellular signaling.

p16(INK4a) prevents centrosome dysfunction and genomic instability in primary cells.

Aneuploidy, frequently observed in premalignant lesions, disrupts gene dosage and contributes to neoplastic progression. Theodor Boveri hypothesized nearly 100 years ago that aneuploidy was due to an increase in centrosome number (multipolar mitoses) and the resultant abnormal segregation of chromosomes. We performed immunocytochemistry, quantitative immunofluorescence, karyotypic analysis, and time-lapse microscopy on primary human diploid epithelial cells and fibroblasts to better understand the mechanism involved in the production of supernumerary centrosomes (more than two microtubule nucleating bodies) to directly demonstrate that the presence of supernumerary centrosomes in genomically intact cells generates aneuploid daughter cells.

Vertebrate Smoothened functions at the primary cilium.

The unanticipated involvement of several intraflagellar transport proteins in the mammalian Hedgehog (Hh) pathway has hinted at a functional connection between cilia and Hh signal transduction. Here we show that mammalian Smoothened (Smo), a seven-transmembrane protein essential for Hh signalling, is expressed on the primary cilium. This ciliary expression is regulated by Hh pathway activity; Sonic hedgehog or activating mutations in Smo promote ciliary localization, whereas the Smo antagonist cyclopamine inhibits ciliary localization.

Plasma alpha 1-acid glycoprotein levels in pregnancy.

One hundred and five determinations of plasma alpha 1-acid glycoprotein (alpha 1AG) levels in 96 women with normal pregnancies were done by an enzyme-linked immunosorbent assay developed in this laboratory. Plasma alpha 1AG levels in pregnant women of all trimesters and 4-10 weeks post-partum period do not differ significantly from those obtained from healthy women of child bearing age. In nine women whose pregnancies were complicated by acute inflammation, plasma levels of alpha 1AG were significantly higher.