HCLS1, also known as hematopoietic cell-specific protein-1 or hematopoietic cell-specific lyn substrate-1, is a versatile actin-binding protein in leukocytes. It is involved in dynamic actin remodeling processes in leukocytes, which are crucial for functions like adhesion, migration, phagocytosis, and granule release. It also participates in signaling pathways downstream of many receptors such as BCR, TCR, and CXCR4, and is important for the activation of GTPases and integrins [1].

HCLS1-deficient mice are neutropenic, demonstrating its importance in myelopoiesis. In severe congenital neutropenia patients with HAX1 gene mutations, there are profound defects in G-CSF-triggered phosphorylation of HCLS1, leading to reduced autoregulation and expression of the transcription factor LEF-1. This indicates that the interaction among HCLS1, HAX1, and LEF-1 proteins is essential for G-CSF-triggered granulopoiesis [2].

In conclusion, HCLS1 is a key protein in leukocyte function and myelopoiesis. Studies on HCLS1-deficient mouse models have revealed its critical role in severe congenital neutropenia, providing insights into the molecular mechanisms underlying this disease and potentially guiding the development of new therapeutic strategies.

References:

1. Castro-Ochoa, Karla F, Guerrero-Fonseca, Idaira M, Schnoor, Michael. 2018. Hematopoietic cell-specific lyn substrate (HCLS1 or HS1): A versatile actin-binding protein in leukocytes. In Journal of leukocyte biology, 105, 881-890. doi:10.1002/JLB.MR0618-212R. https://pubmed.ncbi.nlm.nih.gov/30537294/

2. Skokowa, Julia, Klimiankou, Maxim, Klimenkova, Olga, Grosschedl, Rudolf, Welte, Karl. 2012. Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis. In Nature medicine, 18, 1550-9. doi:10.1038/nm.2958. https://pubmed.ncbi.nlm.nih.gov/23001182/