Abstract: Glial cells can release signal molecules that mediate intercellular communication. In particular，ATP release from astrocytes is required for Ca2+ wave propagation among astrocytes and for feedback modulation of synaptic functions. We found that lysosomes in astrocytes contain abundant ATP and their partial exocytosis resulted in a low-level ATP release，whereas full exocytosis led to the release of a larger amount of ATP，together with lysosomal enzymes. Repetitive neuronal activity induces release of ATP / adenosine from astrocytes，which in turn causes both short-term and long-term hetero-synaptic plasticity. Microglia，resident macrophages in the central nervous system，are responsible for the maintenance of brain homeostasis. Nucleotides have been also found to induce microglial chemotaxis and ingestions，leading to their scavenging of the abnormal materials. We found that nucleotides trigger microglial macropinocytosis by activation of P2Y receptors. Further evidence indicates that the purinemediated microglial macropinocytosis plays an important role in the internalization of soluble proteins and peptides including antigens and beta amyloid. We demonstrated a size-based sorting mechanism of pinosomal luminal cargoes，provides physiological relevance for the kiss-and-run fusion of intracellular organelles，and suggests a refined model for processing and trafficking of exogenous antigen.