A healthy population of mitochondria, maintained by proper fission, fusion, and degradation, is critical for the long-term survival and function of neurons. Here, our discovery of mitophagy intermediates in fission-impaired Drosophila neurons brings new perspective into the relationship between mitochondrial fission and mitophagy. Neurons lacking either the ataxia disease gene Vps13D or the dynamin related protein Drp1 contain enlarged mitochondria that are engaged with autophagy machinery and also lack matrix components. Reporter assays combined with genetic studies imply that mitophagy both initiates and is completed in Drp1 impaired neurons, but fails to complete in Vps13D impaired neurons, which accumulate compromised mitochondria within stalled mito-phagophores. Our findings imply that in fission-defective neurons, mitophagy becomes induced, and that the lipid channel containing protein Vps13D has separable functions in mitochondrial fission and phagophore elongation.
Members of the Vps13 family of proteins have recently been suggested to function in lipid exchange at inter-organelle contact sites. While all family members (VPS13A-D) have been implicated in neurodevelopmental and neurodegenerative diseases, the biological functions of these proteins in neurons are not known. Here we report two cellular functions for the essential gene Vps13D in Drosophila motoneurons: the first is in the initiation of mitochondrial fission; the second is in the progression of selective mitophagy, which becomes induced in neurons as a consequence of the fission defect. Loss of Vps13D in neurons leads to unique mitophagy intermediates that also appear when fission is disrupted simultaneously with impairment to autophagy machinery. This novel identification of intermediates trapped in late stages of mitophagy enables new insight into mechanisms of mitochondrial quality control in neurons in vivo .
B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre-Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B cells in the EF and GC response. Overall, these studies demonstrate that B cells expressing high affinity BCRs preferentially differentiate into antibody secreting cells (ASCs) while those expressing low affinity BCRs undergo further affinity maturation or differentiate into memory B cells (MBCs).
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