Abstract
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.
Highlights
Autophagy: A Brief IntroductionCalled self-eating, a natural and evolutionarily conserved lysosomal degradation and renovation process to hydrolyze unused or dysfunctional cellular components, such as long-lived or misfold proteins and useless organelles [23]
CD38 is a type II membrane protein, originally identified as a cell surface differentiation marker in B lymphocytes, and later found to be expressed ubiquitously [1] [2]
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)
Summary
Called self-eating, a natural and evolutionarily conserved lysosomal degradation and renovation process to hydrolyze unused or dysfunctional cellular components, such as long-lived or misfold proteins and useless organelles [23]. The main and most common pathway, macroautophagy, usually called autophagy, is an intracellular recycling system, used primarily to mediate bulk degradation of superfluous or damaged cytosolic materials [23]. This autophagy processes include several steps: 1) induction and formation of a double membrane vesicle known as an autophagosome, 2) autophagosomes trafficking and fusion with lysosomes to form autolysosomes, and 3) degradation and recycling of autophagic contents via acidic lysosomal hydrolases (Figure 2). In addition to Atg proteins, many other factors and proteins, including Ras-related protein Rab7/5A (Rab7/5A), Lysosomal-associated membrane protein 1/2 (Lamp1/ Lamp2), ATPase, Vacuolin-1, TPCs and TRPMLs have been implicated in regulating autophagosomal lysosomal fusion process [35] [38] [39] [40]. The mechanisms of the control for lysosome function are emerging as an important theme for autophagy-lysosomal cargos digestion
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