The functional characterization of klp-20/vab-6: A gene encoding a kinesin-like protein required for Caenorhabditis elegans embryonic morphogenesis
Motor proteins convert chemical energy to perform mechanical work which cells require for essential activities, such as transporting cargo away from the nucleus. Kinesins are one class of molecular motors which cells use to transport various molecules or entire organelles from one location to another. They play a central role during the building of the cilium which is responsible for various activities including cell signaling. In our model organism Caenorhabditis elegans (C. elegans), the klp-20 gene encodes a kinesin-like protein belonging to the kinesin-2 family of plus-end directed microtubule-based motor proteins. In the worm we refer to the protein encoded by the klp-20 gene as KLP-20 and the human ortholog is KIF3A, encoded by the Kif3a gene. Throughout this thesis, this kinesin motor will be represented by the C. elegans name followed by the human ortholog (KLP-20/KIF3A). There are two members of the kinesin-2 family. The first is Kinesin-II which is a heterotrimeric motor complex which consists of the KLP-20/KIF3A subunit, along with KLP-11/KIF3B and KAP-1/KAP-3. The second member is OSM-3/KIF17. Both Kinesin-II and OSM-3/KIF17 participate in a bidirectional motility transport intraflagellar transport (IFT) needed for ciliogenesis, the building of the cilium. Originally, klp-20 mutants were identified as vab-6 mutants due to their most striking bumpy body variable abnormal (Vab) phenotype. This phenotype can be rescued by expressing klp-20 pan neuronally. Null alleles of klp-11(tm324) and kap-1(ok676) do not show this Vab phenotype, suggesting that KLP-20 may have roles independent of its classical heterotrimeric complex. Expression patterns of the KLP-20 suggests the protein having a strong role in the nervous system. The aim of this study is to characterize the role of KLP-20 and understand how mutations in klp-20 causes defective epidermal morphogenesis. I predict that Kinesin-II functions along microtubules to participate in neuron development and axonal growth and I hope to understand how this could generate the abnormal epidermal phenotype. KLP-20 has a role in the development of amphid sensory neurons and mechanosensory neurons. We hope these findings will allow us to better understand the cell nonautonomous behavior of KLP-20 and ultimately the molecular processes involved in morphogenesis.
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