棕榈酸转移酶催化的蛋白质棕榈酰化广泛存在于神经细胞中，调控神经递质的信号传导，并与多种神经系统疾病发病有关，然而视网膜神经细胞中蛋白质棕榈酰化修饰的研究几乎空白。本课题组率先开展对其中一种PAT酶DHHC16的研究，构建了双极细胞特异性DHHC16基因敲除小鼠Chx10-cre/DHHC16loxp，并发现该小鼠视网膜电图b波异常，据此我们提出“DHHC16棕榈酸酰基转移酶可能通过影响双极细胞中蛋白质棕榈酰化从而影响其对视觉信号的传递”的假设。我们将运用视网膜电图和全细胞膜片钳技术从整体和细胞水平分析DHHC16敲除小鼠中各类双极细胞对光和神经递质反应的异常，并分析其生长、凋亡、衰老和抗氧化应激反应的表现，最后结合棕榈酰化蛋白质组化研究，寻找双极细胞内DHHC16修饰的蛋白质图谱和导致其功能异常的靶蛋白，为深入了解双极细胞视觉信号传递机制提供新的认知，为治疗相关疾病提供新靶点。

Despite the well-known significance of protein palmitoylation in neuronal functions, little is known about protein palmitoylation in the retina or visual signal transduction. Retinal bipolar cells are important in phototransduction. Previously we have shown that one of the palmitoyl acyl transferases, DHHC16, was needed for embryonic eye development. Here we hypothesize that DHHC16 affects the function of bipor cells through the regulation of protein palmitoylation. We constructed a mouse model with bipolar/Muller cell-specific DHHC16 deficiency: Chx10-Cre/DHHC16loxP. Initial studies of these mice revealed significantly reduced b-wave amplitude on electroretinography with signs of defective ON- and OFF-bipolar cell functions. We propose to carry out detailed ERG analysis as well as whole-cell patch clamp studies on retina tissues to further characterize the defects associated with DHHC16 knockout in bipolar cells. We will also study the differentiation, growth, apoptosis and senescence of these cells. We will explore the substrates of DHHC16 by comparing the palmitoylomes between normal and DHHC16 deficient bipolar cells. In addition, we will focus on the palmitoylation of proteins known to be important to the bipolar cell neuron transmitter signal transduction. Taken together, this study will reveal the role of DHHC16 in bipolar cell function and possibly new mechanisms in regulating bipolar cell activity.