All-trans retinoic acid as a versatile cytosolic signal modulator mediated by CRABP1

Isha Nagpal, Li Na Wei

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


All-trans retinoic acid (AtRA), an active metabolite of vitamin A, is recognized for its classical action as an endocrine hormone that triggers genomic effects mediated through nuclear receptors RA receptors (RARs). New evidence shows that atRA-mediated cellular responses are biphasic with rapid and delayed responses. Most of these rapid atRA responses are the outcome of its binding to cellular retinoic acid binding protein 1 (CRABP1) that is predominantly localized in cytoplasm and binds to atRA with a high affinity. This review summarizes the most recent studies of such non-genomic outcomes of atRA and the role of CRABP1 in mediating such rapid effects in different cell types. In embryonic stem cells (ESCs), atRA-CRABP1 dampens growth factor sensitivity and stemness. In a hippocampal neural stem cell (NSC) population, atRA-CRABP1 negatively modulates NSC proliferation and affects learning and memory. In cardiomyocytes, atRA-CRABP1 prevents over-activation of calcium-calmodulin-dependent protein kinase II (CaMKII), protecting heart function. These are supported by the fact that CRABP1 gene knockout (KO) mice exhibit multiple phenotypes including hippocampal NSC expansion and spontaneous cardiac hypertrophy. This indicates that more potential processes/signaling pathways involving atRA-CRABP1 may exist, which remain to be identified.

Original languageEnglish (US)
Article number3610
JournalInternational journal of molecular sciences
Issue number15
StatePublished - Aug 1 2019

Bibliographical note

Funding Information:
Funding: This study was supported by NIH grants DK54733, DK60521, and the Dean’s Commitment and the Distinguished McKnight Professorship of the University of Minnesota to L.-N.W.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


  • All-trans retinoic acid
  • CRABP1
  • CaMKII signaling
  • Cardiomyocyte
  • ESC
  • NSC
  • RAF-MEK signaling


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