A nuclear odyssey: fibroblast growth factor-2 (FGF-2) as a regulator of nuclear homeostasis in the nervous system

Abstract

Nuclear localization of classical growth factors is a well-known phenomenon but still remains a molecular and cellular conundrum. Fibroblast growth factor-2 (FGF-2) is an excellent example of a protein which functions as an extracellular molecule involved in canonical receptor tyrosine kinase signaling as well as displaying intracellular functions. Paracrine and nuclear functions are two important sides of the same protein. FGF-2 is expressed in isoforms with different molecular weights from one mRNA species. In rodents, all of these isoforms become imported to the nucleus. In this review, we discuss structural and functional aspects of FGF-2 isoforms in the nervous system. The nuclear odyssey of FGF-2 is reflected by nuclear dynamics, localization to nuclear bodies such as nucleoli, binding to chromatin and engagement in various protein interactions. Recently discovered molecular partnerships of the isoforms shed light on their nuclear functions, thereby greatly extending our knowledge of the multifaceted functions of FGF-2.

The role of fibroblast growth factor 2 in drug addiction

“…A single Fgf2 transcript can be translated to several isoforms: the secreted low molecular weight isoform (18 kDa) (Reuss & von Bohlen und Halbach, 2003) and the high molecular weight isoforms (21 and 23 kDa), which have a nuclear localization signal. Upon entering the nucleus, the high molecular weight isoforms affect nuclear function such as gene expression (Chlebova et al, 2009;Forthmann et al, 2015). From the early stages of embryonic development, FGF2 is extensively expressed throughout the neuronal tube (Dono et al, 1998;Ford-Perriss et al, 2001).…”

Help-me signaling: Non-cell autonomous mechanisms of neuroprotection and neurorecovery

“…FGF2 is expressed in different isoforms with distinct molecular weights (Forthmann et al 2015). Signaling of FGF2 occurs through the high-affinity tyrosine kinase receptors FGFR1-4 (Jaye et al 1992).…”

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

“…The two highest molecular weight (HMW) isoforms do not exist in rodents. The low molecular weight (LMW) 18 kDa isoform is found both in the nucleolus and cytoplasm and can be secreted, whereas the other four HMW isoforms remain in the nucleus [22]. Thus, the different isoforms can have distinct functions in different regions and exhibit different expression patterns throughout early brain development.…”