Rinl, also known as Ras and Rab interactor (or Ras interaction/interference)-like, is a guanine nucleotide-exchange factor (GEF) for the Rab5 subfamily. The Rab family of small GTPases is crucial in membrane trafficking, and Rinl, with its conserved VPS9 domain, drives the active GTP-bound state of Rab5 subfamily proteins. It is involved in multiple biological processes such as endocytosis and is associated with pathways like the EphA8-degradation pathway and CD28-related signaling pathways [1,2,3].

Loss-of-function studies have provided insights into Rinl's role. In mice, loss of Rinl leads to an increase of T follicular helper (Tfh) cells during aging, upon in vivo immunization, and acute LCMV Armstrong infection, highlighting its role as a negative regulator of Tfh generation. Mechanistically, Rinl regulates CD28 internalization and signaling, which shapes CD4+ T cell activation and differentiation [2].

In conclusion, Rinl is an important GEF that plays a role in membrane-associated processes and cell-signaling pathways. The gene knockout mouse models have revealed its significance in Tfh cell differentiation, emphasizing its potential importance in immunological-related disease areas.

References:

1. Kajiho, Hiroaki, Fukushima, Shinichi, Kontani, Kenji, Katada, Toshiaki. 2012. RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin. In PloS one, 7, e30575. doi:10.1371/journal.pone.0030575. https://pubmed.ncbi.nlm.nih.gov/22291991/

2. Sandner, Lisa, Alteneder, Marlis, Rica, Ramona, Herbst, Ruth, Boucheron, Nicole. 2023. The guanine nucleotide exchange factor Rin-like controls Tfh cell differentiation via CD28 signaling. In The Journal of experimental medicine, 220, . doi:10.1084/jem.20221466. https://pubmed.ncbi.nlm.nih.gov/37703004/

3. Woller, Barbara, Luiskandl, Susan, Popovic, Milica, Rehmann, Holger, Herbst, Ruth. 2011. Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22. In Biochimica et biophysica acta, 1813, 1198-210. doi:10.1016/j.bbamcr.2011.03.005. https://pubmed.ncbi.nlm.nih.gov/21419809/