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Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development
Marlen Breuer1,2, Hanna Berger1, Annette Borchers3,4
1Department of Biology, Molecular Embryology, Philipps-University Marburg, Marburg, Germany.
Abstract:
Caveolins are essential structural proteins driving the formation of caveolae, specialized invaginations of the plasma membrane. Loss of Caveolin-1 (Cav1) function in mice causes distinct neurological phenotypes leading to impaired motor control, however, the underlying developmental mechanisms are largely unknown. In this study we find that loss-of-function of Xenopus Cav1 results in a striking swimming defect characterized by paralysis of the morphants. High-resolution imaging of muscle cells revealed aberrant sarcomeric structures with disorganized actin fibers. As cav1 is expressed in motor neurons, but not in muscle cells, the muscular abnormalities are likely a consequence of neuronal defects. Indeed, targeting cav1 Morpholino oligonucleotides to neural tissue, but not muscle tissue, disrupts axonal outgrowth of motor neurons and causes swimming defects. Furthermore, inhibition of voltage-gated sodium channels mimicked the Cav1 loss-of-function phenotype. In addition, analyzing axonal morphology we detect that Cav1 loss-of-function causes excessive filopodia and lamellipodia formation. Using rescue experiments, we show that the Cav1 Y14 phosphorylation site is essential and identify a role of RhoA, Rac1, and Cdc42 signaling in this process. Taken together, these results suggest a previously unrecognized function of Cav1 in muscle development by supporting axonal outgrowth of motor neurons.
Insights
Loss of Caveolin-1 (Cav1) impairs motor neuron development and causes paralysis in Xenopus. Cav1 is crucial for axonal outgrowth, impacting muscle structure and function.
Area of Science:
- Developmental Biology
- Neuroscience
- Cell Biology
Background:
- Caveolins are vital for forming caveolae, specialized plasma membrane structures.
- Caveolin-1 (Cav1) dysfunction in mice leads to neurological issues and impaired motor control.
- The developmental roles of Cav1, particularly in motor neuron function, remain poorly understood.
Purpose of the Study:
- To investigate the function of Xenopus Caveolin-1 (Cav1) in motor neuron development and muscle function.
- To elucidate the molecular mechanisms underlying Cav1's role in axonal outgrowth and motor control.
Main Methods:
- Xenopus laevis model system for loss-of-function studies using Morpholino oligonucleotides.
- High-resolution imaging to analyze muscle sarcomeric structure and axonal morphology.
- Pharmacological inhibition of voltage-gated sodium channels.
- Rescue experiments to identify critical Cav1 domains and signaling pathways (RhoA, Rac1, Cdc42).
Main Results:
- Cav1 loss-of-function in Xenopus causes severe swimming defects and paralysis.
- Aberrant sarcomeric structures and disorganized actin fibers were observed in muscle cells.
- Targeting Cav1 knockdown to neural tissue, but not muscle, disrupted motor neuron axonal outgrowth.
- Cav1 deficiency led to excessive filopodia and lamellipodia formation in axons.
- The Cav1 Y14 phosphorylation site was essential for normal function, involving RhoA, Rac1, and Cdc42 signaling.
Conclusions:
- Caveolin-1 plays a critical, previously unrecognized role in supporting motor neuron axonal outgrowth.
- Cav1 is essential for proper muscle development and motor control, mediated through its effects on motor neurons.
- Dysregulation of Cav1 impacts cytoskeletal dynamics and neuronal development, leading to motor deficits.
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