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The Polarity/Protusion model of UNC-6/Netrin function in axon repulsion does not rely on a gradient of UNC-6/Netrin. Instead, the UNC-5 receptor polarizes the VD growth cone such that filopodial protrusions are biased to the dorsal leading edge. UNC-5 then inhibits growth cone protrusion ventrally based upon this polarity, resulting in dorsally-biased protrusion and dorsal migration away from UNC-6/Netrin. While previous studies have shown that UNC-5 inhibits growth cone protrusion by destabilizing actin, preventing microtubule + end entry, and preventing vesicle fusion, the signaling pathways involved are unclear. The SRC-1 tyrosine kinase has been previously shown to physically interact with and phosphorylate UNC-5, and to act with UNC-5 in axon guidance and cell migration. Here, the role of SRC-1 in VD growth cone polarity and protrusion is investigated. A precise deletion of src-1 was generated, and mutants displayed unpolarized growth cones with increased size, similar to unc-5 mutants. Transgenic expression of src-1(+) in VD/DD neurons resulted in smaller growth cones, and rescued growth cone polarity defects of src-1 mutants, indicating cell-autonomous function. Transgenic expression of a putative kinase-dead src-1(D831A) mutant caused a phenotype similar to src-1 loss-of-function, suggesting that this is a dominant negative mutation. The D381A mutation was introduced into the endogenous src-1 gene by genome editing, which also had a dominant-negative effect. Genetic interactions of src-1 and unc-5 suggest they act in the same pathway on growth cone polarity and protrusion, but might have overlapping, parallel functions in other aspects of axon guidance. src-1 function was not required for the effects of activated myr::unc-5, suggesting that SRC-1 might be involved in UNC-5 dimerization and activation by UNC-6, of which myr::unc-5 is independent. In sum, these results show that SRC-1 acts with UNC-5 in growth cone polarity and inhibition of protrusion.
Pubmed ID: 38771761
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Database of biological data related to a single initiative, originating from a single organization or from a consortium. A BioProject record provides users a single place to find links to the diverse data types generated for that project. It is a searchable collection of complete and incomplete (in-progress) large-scale sequencing, assembly, annotation, and mapping projects for cellular organisms. Submissions are supported by a web-based Submission Portal. The database facilitates organization and classification of project data submitted to NCBI, EBI and DDBJ databases that captures descriptive information about research projects that result in high volume submissions to archival databases, ties together related data across multiple archives and serves as a central portal by which to inform users of data availability. BioProject records link to corresponding data stored in archival repositories. The BioProject resource is a redesigned, expanded, replacement of the NCBI Genome Project resource. The redesign adds tracking of several data elements including more precise information about a project''''s scope, material, and objectives. Genome Project identifiers are retained in the BioProject as the ID value for a record, and an Accession number has been added. Database content is exchanged with other members of the International Nucleotide Sequence Database Collaboration (INSDC). BioProject is accessible via FTP.
View all literature mentionsSoftware tool for sequence mapping.The next version of BWA-MEM. Used for aligning sequencing reads against large reference genome.
View all literature mentionsCenter that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
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