No abstract

Dedicator of cytokinesis 10 (DOCK10) is a guanine nucleotide exchange factor (GEF) belonging to the DOCK family that activate RHO GTPases. DOCK10 controls amoeboid migration and IL-4 induced B cell activation. Recent structural studies of the catalytic DHR2 domains of DOCK-family GEFs DOCK2 and DOCK9 in the presence of nucleotide-free RAC and CDC42 respectively, have revealed a conserved mechanism of nucleotide exchange distinct from the large family of Dbl homology (DH) GEFs. Less is known from a biochemical and structural perspective, about DOCK10. We have determined the crystal structure of the apo-state of the DHR2 domain of DOCK10 (DOCK10DHR2), which provides the first structural model for the apo-state of a DHR2 domain for the entire DOCK family. It demonstrates the conformational changes within DOCK10DHR2 on engaging the GTPase, and associated induced conformational changes of the GTPase required to stimulate nucleotide release. We also report on the unexpected dual specificity of DOCK10DHR2 which directly interacts with RAC and CDC42 and induces the nucleotide exchange of both in vitro. This dual specificity is unique to DOCK10 within its evolutionarily related D subfamily. Structural studies of DOCK10DHR2 complex with RAC revealed an intriguing 2:1 stoichiometry between DOCK10DHR2 and the GTPase, that differs from the canonical 1:1 stoichiometry for all other known DOCK-GTPase complexes. This was confirmed in solution using a variety of biophysical techniques. The identification of a novel mode of interaction between DOCK10DHR2 and the RAC GTPase provides new insights into how DOCK family GEFs discriminate between CDC42, RAC and RHOA.

Nowadays, the development of the Internet makes it easy for Chinese teenagers to know something about sex. And teenagers begin to be curious and concerned about sexual detail because of physiological maturation in adolescence. However, sex education is a sensitive area for some parents, so that Chinese parents often interrupt or accuse teenagers when they have some issues about sex. The late data shows that when parents responded by avoiding the question about sex in families, the teenager will have a negative attitude toward sex. The purpose of this study that makes Chinese parents realize the importance of sex education in families first. In addition, Chinese parents need to actively change their ways and to conduct systematic and scientific sex education for children in families. It will be so helpful that teenagers can grow up healthily. The pertinent literature was collected and analyzed in the electronic database, so we think about sex education in Chinese families today based on the theory of Satir’s Iceberg.  Therefore, parents that have children in adolescence should transform their views and coping styles so that real sexual values will be sent to teenagers in a healthy way.