{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CALML4, a small calmodulin‐like protein containing EF‐hand motifs, appears to have multifaceted roles that vary with cellular context. In intestinal epithelial cells, CALML4 is highly enriched at the distal tips of microvilli where it directly binds to myosin‐7b, functioning as its light chain and contributing to the assembly and maintenance of the intermicrovillar adhesion complex. Its association with myosin‐7a further suggests a role in the organization of sensory protein complexes related to the Usher syndrome network."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the neural context, CALML4 expression is modulated under several conditions. In the murine neonate brain, a knockout of HDAC4 results in a significant decrease in CALML4 expression, implying that its transcription may be regulated by HDAC4‐dependent pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Furthermore, CALML4 is down‐regulated in the hippocampus of stress‐exposed neonatal mice following repeated morphine administration, suggesting that reduced levels of CALML4 might be linked to altered neurodevelopmental or synaptic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CALML4 has also emerged as a candidate factor in disease prognosis and differentiation. In a gastric cancer gene expression network, higher CALML4 levels are associated with better clinical outcomes, pointing to a potential tumor‐suppressive or prognostic role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, in a model of depression treated with a traditional Chinese herbal decoction, CALML4 is among several differentially expressed mRNAs that overlap between in vivo and in vitro studies, hinting at its involvement in signaling pathways that affect neurotransmitter balance and neurotrophic support."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, during chondrogenic differentiation in the ATDC5 mouse chondroprogenitor cell line, CALML4 is one of a set of highly regulated genes, suggesting that it may contribute to the molecular events underlying cartilage formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies underscore that CALML4 functions in a context-dependent manner—contributing structurally to brush border assembly in the gut, while also being implicated in neurodevelopment, cellular stress responses, cancer prognosis, and cartilage differentiation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Myoung Soo Choi, Maura J Graves, Samaneh Matoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The small EF-hand protein CALML4 functions as a critical myosin light chain within the intermicrovillar adhesion complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.012820"}], "href": "https://doi.org/10.1074/jbc.RA120.012820"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32209652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32209652"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michal Mielcarek, Tamara Seredenina, Matthew P Stokes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC4 does not act as a protein deacetylase in the postnatal murine brain in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0080849"}], "href": "https://doi.org/10.1371/journal.pone.0080849"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24278330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24278330"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryan M McAdams, Ronald J McPherson, Richard P Beyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dose-dependent effects of morphine exposure on mRNA and microRNA (miR) expression in hippocampus of stressed neonatal mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0123047"}], "href": "https://doi.org/10.1371/journal.pone.0123047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25844808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25844808"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ping Yang, Junjie Liu, Tianci Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Integrated analysis of the chemical-material basis and molecular mechanisms for the classic herbal formula of Lily Bulb and Rehmannia Decoction in alleviating depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chin Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13020-021-00519-x"}], "href": "https://doi.org/10.1186/s13020-021-00519-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34674715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34674715"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Li Chen, Trine Fink, Xiao-Yan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative transcriptional profiling of ATDC5 mouse progenitor cells during chondrogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Differentiation (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1432-0436.2005.00038.x"}], "href": "https://doi.org/10.1111/j.1432-0436.2005.00038.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16219039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16219039"}]}]}]}