FEZ1 Forms Complexes with CRMP1 and DCC to Regulate Axon and Dendrite Development
| Autor: | Jie Yin Chua, Shi Jun Ng, John Jia En Chua, Erich E. Wanker, Oleksandr Yagensky |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Deleted in Colorectal Cancer
Growth Cones Nerve Tissue Proteins Receptors Cell Surface Dendrite Development Biology dendrite Biological neural network medicine Animals Axon Growth cone Adaptor Proteins Signal Transducing DCC Neurons axon CRMP1 General Neuroscience SEMA3A General Medicine DCC Receptor FEZ1 Axons Rats medicine.anatomical_structure nervous system Neuroscience Research Article: New Research |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| Popis: | Elaboration of neuronal processes is an early step in neuronal development. Guidance cues must work closely with intracellular trafficking pathways to direct expanding axons and dendrites to their target neurons during the formation of neuronal networks. However, how such coordination is achieved remains incompletely understood. Here, we characterize an interaction between fasciculation and elongation protein zeta 1 (FEZ1), an adapter involved in synaptic protein transport, and collapsin response mediator protein (CRMP)1, a protein that functions in growth cone guidance, at neuronal growth cones. We show that similar to CRMP1 loss-of-function mutants, FEZ1 deficiency in rat hippocampal neurons causes growth cone collapse and impairs axonal development. Strikingly, FEZ1-deficient neurons also exhibited a reduction in dendritic complexity stronger than that observed in CRMP1-deficient neurons, suggesting that the former could partake in additional developmental signaling pathways. Supporting this, FEZ1 colocalizes with VAMP2 in developing hippocampal neurons and forms a separate complex with deleted in colorectal cancer (DCC) and Syntaxin-1 (Stx1), components of the Netrin-1 signaling pathway that are also involved in regulating axon and dendrite development. Significantly, developing axons and dendrites of FEZ1-deficient neurons fail to respond to Netrin-1 or Netrin-1 and Sema3A treatment, respectively. Taken together, these findings highlight the importance of FEZ1 as a common effector to integrate guidance signaling pathways with intracellular trafficking to mediate axo-dendrite development during neuronal network formation. |
| Databáze: | OpenAIRE |
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