Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response

Aloor, Jim J.; Azzam, Kathleen M.; Guardiola, John; Gowdy, Kymberly M.; Madenspacher, Jennifer H.; Gabor, Kristin A.; Mueller, Geoffrey A.; Lin, Wan-Chi; Lowe, Julie M.; Gruzdev, Artiom; Draper, David E.; Merrick, B. Alex; Fessler, Michael B.

doi:10.1074/jbc.ra118.004300

Cited by 18 publications

(24 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Monocyte-derived dendritic cells (DCs) stimulated with lipopolysaccharide (LPS) induce a negative feedback loop of cytokine production via microRNA-155 that affects LRCH3 and LRCH4 expression levels, which is in line with findings in HEK293 cells showing increased LRCH3 levels upon stimulation with Epstein-Barr virus latent membrane protein (LMP1) (Ceppi et al, 2009;Gewurz et al, 2011). In human platelets exposed to E. coli K12 and RAW 264.7 macrophages stimulated with LPS LRCH4 mRNA levels are downregulated (Fejes et al, 2018;Aloor et al, 2019). Microglia isolated from rat spinal cords after spinal cord injury (SCI) express lower levels of LRCH1 mRNA and protein compared to microglia from sham-operated rats (Chen et al, 2020).…”

Section: Transcriptional Analyses In Immune Responsessupporting

confidence: 69%

“…The structure of the four members of the human (h)LRCH proteins characterized by an N-terminal LRR domain and a C-terminal CH domain is shown in Figure 1A (Foussard et al, 2010). In addition to the unique combination of LRR and CH domains, a putative transmembrane (TM) domain within the C-terminus has been described for LRCH1 and LRCH4 (Ng et al, 2011;Aloor et al, 2019). Sequence alignments of all four human LRCH proteins revealed modest sequence identity ranging between 33.1 and 39.4%.…”

Section: Structure Of Lrch Proteinsmentioning

confidence: 99%

“…LRCH proteins exist in different isoforms with two of three hLRCH1 and the longest isoforms of hLRCH4 and murine (m)LRCH4 presenting a putative TM domain at their C-terminus (Ng et al, 2011;Aloor et al, 2019). A search using the Phobius software for prediction of transmembrane topology 1 further revealed the existence of a putative TM domain in the longest isoform of hLRCH3 and rat LRCH4, but experimental evidence for this observation is missing (Käll et al, 2007).…”

Section: Transmembrane Domainmentioning

confidence: 99%

See 2 more Smart Citations

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Rivière

Bader

Pogoda

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Actin-dependent leukocyte trafficking and activation are critical for immune surveillance under steady state conditions and during disease states. Proper immune surveillance is of utmost importance in mammalian homeostasis and it ensures the defense against pathogen intruders, but it also guarantees tissue integrity through the continuous removal of dying cells or the elimination of tumor cells. On the cellular level, these processes depend on the precise reorganization of the actin cytoskeleton orchestrating, e.g., cell polarization, migration, and vesicular dynamics in leukocytes. The fine-tuning of the actin cytoskeleton is achieved by a multiplicity of actin-binding proteins inducing, e.g., the organization of the actin cytoskeleton or linking the cytoskeleton to membranes and their receptors. More than a decade ago, the family of leucine-rich repeat (LRR) and calponin homology (CH) domain-containing (LRCH) proteins has been identified as cytoskeletal regulators. The LRR domains are important for protein-protein interactions and the CH domains mediate actin binding. LRR and CH domains are frequently found in many proteins, but strikingly the simultaneous expression of both domains in one protein only occurs in the LRCH protein family. To date, one LRCH protein has been described in drosophila and four LRCH proteins have been identified in the murine and the human system. The function of LRCH proteins is still under investigation. Recently, LRCH proteins have emerged as novel players in leukocyte function. In this review, we summarize our current understanding of LRCH proteins with a special emphasis on their function in leukocyte biology.

show abstract

Section: Transcriptional Analyses In Immune Responsessupporting

confidence: 69%

Section: Structure Of Lrch Proteinsmentioning

confidence: 99%

Section: Transmembrane Domainmentioning

confidence: 99%

See 1 more Smart Citation

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Rivière

Bader

Pogoda

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Lrch4 is a plasma membrane protein abundantly expressed in the spleen and thymus, containing a single-pass transmembrane domain with nine leucine-rich repeats and a CH3 domain in its ectodomain (Aloor et al, 2019). Recent data showed that Lrch4 did not interact with ezrin, radixin and moesin (ERM) in drosophila S2 cells, suggesting that the CH3 domain of Lrch4 may not bind with the FERM domain of ERM (Foussard et al, 2010).…”

Section: Lrch4mentioning

confidence: 99%

Structural Characteristics, Binding Partners and Related Diseases of the Calponin Homology (CH) Domain

Yin

Schnoor

Jun

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The calponin homology (CH) domain is one of the most common modules in various actin-binding proteins and is characterized by an α-helical fold. The CH domain plays important regulatory roles in both cytoskeletal dynamics and signaling. The CH domain is required for stability and organization of the actin cytoskeleton, calcium mobilization and activation of downstream pathways. The CH domain has recently garnered increased attention due to its importance in the onset of different diseases, such as cancers and asthma. However, many roles of the CH domain in various protein functions and corresponding diseases are still unclear. Here, we review current knowledge about the structural features, interactome and related diseases of the CH domain.

show abstract

“…LRCH1, belonging to the LRCH proteins family, contains LRRs motifs and CH domains, and is widely expressed in heart, spleen, thymus, and intestine [34]. LRR motifs display a rapid diversification and have been implicated in protein-ligand and protein-protein interactions [35,36]. CH domains are well established as protein domains mediating interaction with actin filaments [34,37].…”

Section: Discussionmentioning

confidence: 99%

LRCH1 suppresses migration of CD4⁺ T cells and refers to disease activity in ulcerative colitis

Wang¹,

Zhang²,

He³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

Background: Ulcerative colitis (UC) is a chronically remittent and progressive inflammatory disorder. LRCH1 is reported to be involved in the immune-regulation of several diseases. However, the exact roles of LRCH1 in UC are still obscure. Materials and Methods: LRCH1 expression was analyzed in the inflamed mucosa and peripheral blood mononuclear cells (PBMCs) from patients with UC by quantitative RT-PCR and immunohistochemistry. Peripheral blood CD4 + T cells were transfected with lentivirus-expressing LRCH1 (LV-LRCH1) or LV-sh-LRCH1, and cytokine expression was determined by using flow cytometry, quantitative RT-PCR and ELISA. Transfected CD4 + T cells were harvested to examine the capacity of chemotaxis using Transwell plate. Results: LRCH1 expression was highly decreased in colonic mucosa and PBMCs from patients with A-UC, and negatively correlated with disease activity. Up or down regulation of LRCH1 did not affect the differentiation of CD4 + T cells, and the related cytokines expression. Moreover, LRCH1 inhibited migratory capacity of CD4 + T cells toward CXCL12 by PKCα. Conclusion: LRCH1 plays an important role in the pathogenesis of UC, possibly through modulating the migration of CD4 + T cells. Therefore, targeting LRCH1 might serve as a novel therapeutic approach in the management of UC.

show abstract

Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response

Cited by 18 publications

References 51 publications

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Structural Characteristics, Binding Partners and Related Diseases of the Calponin Homology (CH) Domain

LRCH1 suppresses migration of CD4⁺ T cells and refers to disease activity in ulcerative colitis

Contact Info

Product

Resources

About

Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response

Cited by 18 publications

References 51 publications

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Structural Characteristics, Binding Partners and Related Diseases of the Calponin Homology (CH) Domain

LRCH1 suppresses migration of CD4+ T cells and refers to disease activity in ulcerative colitis

Contact Info

Product

Resources

About

LRCH1 suppresses migration of CD4⁺ T cells and refers to disease activity in ulcerative colitis