Homeodomain-interacting protein kinase (Hipk) plays roles in nervous system and muscle structure and function

• Published in: PloS one Vol. 15; no. 3; p. e0221006
• Main Authors: Wang, Simon J H, Sinclair, Donald A R, Kim, Hae-Yoon, Kinsey, Stephen D, Yoo, Byoungjoo, Shih, Claire R Y, Wong, Kenneth K L, Krieger, Charles, Harden, Nicholas, Verheyen, Esther M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-03-2020; Public Library of Science (PLoS)
• Subjects: Adducin; Animals; Binding proteins; Biochemistry; Biology and Life Sciences; Body Patterning; Ca2+/calmodulin-dependent protein kinase II; Calcium; Calcium binding proteins; Calcium-binding protein; Calmodulin; Cell Nucleus - metabolism; Cell proliferation; Cytoskeleton; Deoxyribonucleic acid; Diseases; DNA; DNA-binding protein; Dopamine receptors; Drosophila; Drosophila melanogaster - anatomy & histology; Drosophila melanogaster - enzymology; Drosophila melanogaster - physiology; Drosophila Proteins - isolation & purification; Drosophila Proteins - metabolism; Eye - embryology; Fruit flies; Gene expression; Genetic engineering; Glial cells; Homeobox; Insects; Kinases; Kinesiology; Larva - metabolism; Lethality; Male; Males; Medicine and Health Sciences; Molecular biology; Motor neuron diseases; Muscles; Muscles - anatomy & histology; Muscles - cytology; Muscles - metabolism; Nervous system; Nervous System - anatomy & histology; Nervous System - cytology; Nervous System - metabolism; Neuromuscular Junction - metabolism; Neuromuscular junctions; Neuronal-glial interactions; Neurons; Organ Size; Overexpression; Phosphorylation; Physiology; Protein binding; Protein kinases; Protein Kinases - isolation & purification; Protein structure; Proteinase-activated receptor 1; Proteins; Research and Analysis Methods; Structure (Literature); Structure-function relationships; Synapses - metabolism; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221006

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.