Unknown

Dataset Information

0

Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development


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.

SUBMITTER: Breuer M 

PROVIDER: S-EPMC7536398 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2747223 | biostudies-literature
| S-EPMC3434160 | biostudies-literature
| S-EPMC5101602 | biostudies-literature
| S-EPMC4820394 | biostudies-literature
| S-EPMC4982812 | biostudies-literature
| S-EPMC5405110 | biostudies-literature
| S-EPMC6794869 | biostudies-other
| S-EPMC6650578 | biostudies-literature
| S-EPMC3828348 | biostudies-literature
| S-EPMC7054680 | biostudies-literature