Actin-Independent Behavior and Membrane Deformation Exhibited by the Four-Transmembrane Protein M6a

M6a is a four-transmembrane protein that is abundantly expressed in the nervous system. Previous studies have shown that over-expression of this protein induces various cellular protrusions, such as neurites, filopodia, and dendritic spines. In this detailed characterization of M6a-induced structures, we found their varied and peculiar characteristics. Notably, the M6ainduced protrusions were mostly devoid of actin filaments or microtubules and exhibited free random vibrating motion. Moreover, when an antibody bound to M6a, the membrane-wrapped protrusions were suddenly disrupted, leading to perturbation of the surrounding membrane dynamics involving phosphoinositide signaling. During single-molecule analysis, M6a exhibited cytoskeleton-independent movement and became selectively entrapped along the cell perimeter in an actin-independent manner. These observations highlight the unusual characteristics of M6a, which may have

An Okhotsk adult female human skeleton (11th/12th century AD) with possible SAPHO syndrome from Hamanaka 2 site, Rebun Island, northern Japan

We present the oldest human skeletal case yet identified with possible SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), a chronic disease involving the skin, bone, and joints. A human skeleton with a severe pathological condition was recovered from a shell mound of the prehistoric Okhotsk culture at the Hamanaka 2 site, Rebun Island, Hokkaido, Japan in 2013. Morphological and Amelogenin gene analyses determined the sex as female, and the age at time of death was estimated to be in the forties using analysis of the auricular surface of the ilium. The stable isotope ratios of this individual (NAT002) and other Hamanaka 2 samples indicated a heavy dependence on marine mammals and fish for dietary protein intake. Radiocarbon age on collagen from the bone of NAT002 was 1689 ± 20 BP, or 1060–1155 (68.2%) calAD. Macroscopic and computed tomography (CT) findings indicated diffuse hyperostosis in the axial and appendicular skeleton, including the mandible, vertebrae, clavicles, sternum, scapulae, humeri, radii, ulnae, and ilium, caused by osteitis and synovitis. The bilateral clavicles were most affected, in which CT imaging revealed irregular cortical thickening, termed ‘grotesque periostitis.’ The case was diagnosed as most likely having SAPHO syndrome, although dermatological findings could not be detected. Although SAPHO syndrome is a fairly new concept in autoimmune diseases, this case suggests the syndrome originated much earlier in human history