Cell division control protein 42 homolog (Cdc42) Regulates T Cell Microvilli Formation and Antigen Recognition During T cell development

Abstract

T cell surfaces are covered with actin-rich finger-like membrane protrusions called microvilli, which play a sensory role to survey the surfaces of antigen-presenting cells (APCs). However, it is completely unknown how microvilli are organized during early developmental process of T cells. Here, we report that cell division control protein 42 homolog (Cdc42), which is known to be involved in cell cycle and cell migration, plays a pivotal role in microvilli formation of single-positive (SP) thymocytes. Thymocytes in the double-positive (DP) stage and before have shorter and fewer microvilli, whereas thymocytes in SP stage have much longer and higher numbers of surface microvilli. However, conditional knockout (cKO) of Cdc42 gene (Cdc42f/fCD4cre) showed dramatic reduction of microvilli, in consistent with the reduced expression of TCRs and many microvilli-associated proteins, on the surface of SP thymocytes. Interestingly, single-cell analysis revealed that the population of CCR7—a protein expressed on the surface of naïve T cells—positive cells is seriously affected, and as a result, the exit of mature naïve T cells from the thymus to the periphery was retarded. Taken together, we present the first evidence that the number and size of microvilli is organized and maintained during the period of DP to SP thymocyte maturation by the action of Cdc42.