RRC ID 58533
Author Wang SJH, Sinclair DAR, Kim HY, Kinsey SD, Yoo B, Shih CRY, Wong KKL, Krieger C, Harden N, Verheyen EM.
Title Homeodomain-interacting protein kinase (Hipk) plays roles in nervous system and muscle structure and function.
Journal PLoS One
Abstract Homeodomain-interacting protein kinases (Hipks) have been previously associated with cell proliferation and cancer, however, their effects in the nervous system are less well understood. We have used Drosophila melanogaster to evaluate the effects of altered Hipk expression on the nervous system and muscle. Using genetic manipulation of Hipk expression we demonstrate that knockdown and over-expression of Hipk produces early adult lethality, possibly due to the effects on the nervous system and muscle involvement. We find that optimal levels of Hipk are critical for the function of dopaminergic neurons and glial cells in the nervous system, as well as muscle. Furthermore, manipulation of Hipk affects the structure of the larval neuromuscular junction (NMJ) by promoting its growth. Hipk regulates the phosphorylation of the synapse-associated cytoskeletal protein Hu-li tai shao (Hts; adducin in mammals) and modulates the expression of two important protein kinases, Calcium-calmodulin protein kinase II (CaMKII) and Partitioning-defective 1 (PAR-1), all of which may alter neuromuscular structure/function and influence lethality. Hipk also modifies the levels of an important nuclear protein, TBPH, the fly orthologue of TAR DNA-binding protein 43 (TDP-43), which may have relevance for understanding motor neuron diseases.
Volume 15(3)
Pages e0221006
Published 2020-3-18
DOI 10.1371/journal.pone.0221006
PII PONE-D-19-21142
PMID 32187190
PMC PMC7080231
MeSH Animals Body Patterning Cell Nucleus / metabolism Drosophila Proteins / isolation & purification* Drosophila Proteins / metabolism Drosophila melanogaster / anatomy & histology Drosophila melanogaster / enzymology* Drosophila melanogaster / physiology* Eye / embryology Larva / metabolism Male Muscles / anatomy & histology* Muscles / cytology Muscles / metabolism* Nervous System / anatomy & histology* Nervous System / cytology Nervous System / metabolism* Neuromuscular Junction / metabolism Organ Size Phosphorylation Protein Kinases / isolation & purification* Synapses / metabolism
IF 2.74
Times Cited 0
Drosophila 17090R-1