Structure and Functions of Sidekicks

Abstract

Many of the immunoglobulin superfamily (IgSF) molecules play pivotal roles in cell communication. The Sidekick (Sdk) gene, first described in Drosophila, encodes the single-pass transmembrane protein, Sdk, which is one of the largest among IgSF membrane proteins. Sdk first appeared in multicellular animals during the Precambrian age and later evolved to Sdk1 and Sdk2 in vertebrates by gene duplication. In flies, a single Sdk is involved in positioning photoreceptor neurons and their axons in the visual system and is responsible for dynamically rearranging cell shapes by strictly populating tricellular adherens junctions in epithelia. In vertebrates, Sdk1 and Sdk2 are expressed by unique sets of cell types and distinctively participate in the formation and/or maintenance of neural circuits in the retina, indicating that they are determinants of synaptic specificity. These functions are mediated by specific homophilic binding of their ectodomains and by intracellular association with PDZ scaffold proteins. Recent human genetic studies as well as animal experiments implicate that Sdk genes may influence various neurodevelopmental and psychiatric disorders, such as autism spectrum disorders, attention-deficit hyperactivity disorder, addiction, and depression. The gigantic Sdk1 gene is susceptible to erratic gene rearrangements or mutations in both somatic and germ-line cells, potentially contributing to neurological disorders and some types of cancers. This review summarizes what is known about the structure and roles of Sdks.

Loss of a newly discovered microRNA in Chinese hamster ovary cells leads to upregulation of N‐glycolylneuraminic acid sialylation on monoclonal antibodies

“…Especially during retina development, Gfi-1 is required for terminal retinal ganglion cell differentiation and survival, which is in good agreement with a regulatory Gfi-1 binding site upstream of the SDK1 gene conferring synaptic layer specificity of some retinal ganglion cells by specific cell-cell interactions (Yamagata, 2020;Yang et al, 2003). Conclusively, Gfi-1 has essential roles in hematopoietic cell and sensory organ development but its expression might not be required by CHO cells.…”

“…They share a highly conserved domain organization with a signal sequence, 6 immunoglobulin (Ig) T A B L E 1 Twenty-seven miR-111 anti-correlated genes are found to be associated with protein glycosylation (via Metabolic pathway, GO-biological process and/or Pfam motif annotation) domains, 13 fibronectin type III (FNIII) domains, a transmembrane domain, and a cytoplasmic part (Yamagata, 2020). In particular, the four N-terminal Ig domains mediate specific cell-cell interactions between SDK positive cells facilitating, for example, synaptic layer specificity of ganglion cells during retina development (Goodman et al, 2016;Honig & Shapiro, 2020;Sanes & Yamagata, 1999Yamagata, 2020). However, some FNIII domain containing proteins show lectin-like properties with certain carbohydrate binding specificity (Kleene et al, 2001;Yamagata et al, 2002).…”

“…So far, the reason for the CMAH negative phenotype of CHO production cell lines remained unidentified. However, we were able to provide several lines of evidence that the newly discovered and CHO-specific (cgr-)miRNA-111, which was SDK1 and its homolog SDK2 are among the largest within the group of immunoglobulin superfamily molecules, which facilitate cellular functions as surface receptors, co-receptors, co-effectors, or adhesion molecules (Yamagata, 2020). They share a highly conserved domain organization with a signal sequence, 6 immunoglobulin (Ig) T A B L E 1 Twenty-seven miR-111 anti-correlated genes are found to be associated with protein glycosylation (via Metabolic pathway, GO-biological process and/or Pfam motif annotation) domains, 13 fibronectin type III (FNIII) domains, a transmembrane domain, and a cytoplasmic part (Yamagata, 2020).…”

“…However, we were able to provide several lines of evidence that the newly discovered and CHO-specific (cgr-)miRNA-111, which was SDK1 and its homolog SDK2 are among the largest within the group of immunoglobulin superfamily molecules, which facilitate cellular functions as surface receptors, co-receptors, co-effectors, or adhesion molecules (Yamagata, 2020). They share a highly conserved domain organization with a signal sequence, 6 immunoglobulin (Ig) T A B L E 1 Twenty-seven miR-111 anti-correlated genes are found to be associated with protein glycosylation (via Metabolic pathway, GO-biological process and/or Pfam motif annotation) domains, 13 fibronectin type III (FNIII) domains, a transmembrane domain, and a cytoplasmic part (Yamagata, 2020). In particular, the four N-terminal Ig domains mediate specific cell-cell interactions between SDK positive cells facilitating, for example, synaptic layer specificity of ganglion cells during retina development (Goodman et al, 2016;Honig & Shapiro, 2020;Sanes & Yamagata, 1999Yamagata, 2020).…”

SDK1-ALK Fusion in a Lung Adenocarcinoma Patient With Excellent Response to ALK Inhibitor Treatment: A Case Report

“…The specific function of SDK1 in NSCLC still needs further study. The homophilic binding of Sdk1 ectodomain regions is required for cell-cell aggregation (18). Mutations in SDK1 gene have been found in the lung tissue of asbestos-exposed patients and cancer specimens of stage I lung adenocarcinoma, which may be responsible for dysfunction of cell adhesion in tumor progression (19,20).…”