AG Optobiology, Institute of Biology, Humboldt Universität zu Berlin , Berlin, Germany.
AG "Neuronal Protein Transport", Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany.
J Cell Biol. 2025 Jan 6;224(1). doi: 10.1083/jcb.202403141. Epub 2024 Nov 4.
In mammalian axon-carrying-dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons are preserved. By using dissociated hippocampal cultures as a model, we show that the development of AcD morphology can occur prior to synaptogenesis and independently of the in vivo environment. A single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the soma-derived AIS and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, it does not undergo homeostatic plasticity, contains lesser cisternal organelles, and receives fewer inhibitory inputs. Our findings reveal insights into AcD neuron biology and underscore AIS structural differences based on axon onset.
在哺乳动物轴突携带树突（AcD）神经元中，轴突从基底树突而不是从胞体发出，从而在轴突起始段（AIS）产生动作电位的优势途径。然而，目前尚不清楚如何建立这种不寻常的形态，以及 AcD 神经元中 AIS 的结构和功能是否得到保留。通过使用分离的海马培养物作为模型，我们表明 AcD 形态的发育可以在突触发生之前发生，并且独立于体内环境。单个前体细胞突起首先产生轴突，然后产生 AcD。AIS 具有与源自胞体的 AIS 相似的细胞骨架结构，并同样作为运输障碍来保留轴突特异性的分子组成。然而，它不会经历稳态可塑性，包含较少的内质网细胞器，并且接收较少的抑制性输入。我们的发现揭示了 AcD 神经元生物学的新见解，并强调了基于轴突起始的 AIS 结构差异。
