Dual Roles of CD38 in Autophagy

• 作者: Buqun Fan Jiaxing Song Xiameng Mode Xianwang Wang Zijun Wu
• 来源期刊: 长江医药(英文)
• 学科: 医学
• 关键词: CD38 AUTOPHAGY CALCIUM NAADP LYSOSOME AUTOPHAGOSOME
• 年，卷（期）: cjyyyw_2017,（1）
• 页码范围: 8-19
• 页数: 12页
• 分类号: R73

摘要

CD38 is a versatile, ubiquitously expressed protein that was identified as a multifunctional enzyme. Recently, cumulating evidence has suggested that CD38 is involved in autophagy, which is an evolutionarily conserved lysosomal degradation and recycling system. Acting as a enzyme, CD38 utilizes nicotinamide adenine dinucleotide phosphate (NADP) to synthesize nicotinic acid adenine dinucleotide phosphate (NAADP), which acts as a key messenger for Ca2+-mobilizing in lysosome by targeting two-pore channels (TPCs) or transient receptor potential mucolipins (TRPMLs). Multiple studies have indicated that CD38 is involved in autophagy by modulating intracellular Ca2+ signaling. However, the control of autophagy by CD38 signaling is the subject of two contrary views. The autophagosomes trafficking and fusion with lysosomes to form autolysosomes are crucial steps in autophagy. On the one hand, the avail-able evidence indicates that lysosome trafficking and fusion to autophagosomes is positively modulated by CD38. On the other hand, overexpression of TPC2, which is positively modulated by CD38, was shown to promote the accumulation of autophagosomes, thus suppress autophagy. This review will reveal the interesting contrary dual roles of CD38 in autophagy, and critical insight into the molecular mechanisms of CD38 in autophagy regulation.