Specificity and Redundancy of Profilin 1 and 2 Function in Brain Development and Neuronal Structure

Abstract

Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of more than one profilin isoform in most tissues. In neuronal precursors and in neurons, profilin 1 and profilin 2 are co-expressed, but their specific and redundant functions in brain morphogenesis are still unclear. Using a conditional knockout mouse model to inactivate both profilins in the developing CNS, we found that threshold levels of profilin are necessary for the maintenance of the neuronal stem-cell compartment and the generation of the differentiated neurons, irrespective of the specific isoform. During embryonic development, profilin 1 is more abundant than profilin 2; consequently, modulation of profilin 1 levels resulted in a more severe phenotype than depletion of profilin 2. Interestingly, the relevance of the isoforms was reversed in the postnatal brain. Morphology of mature neurons showed a stronger dependence on profilin 2, since this is the predominant isoform in neurons. Our data highlight redundant functions of profilins in neuronal precursor expansion and differentiation, as well as in the maintenance of pyramidal neuron dendritic arborization. The specific profilin isoform is less relevant; however, a threshold profilin level is essential. We propose that the common activity of profilin 1 and profilin 2 in actin dynamics is responsible for the observed compensatory effects.

Transient reduction in dendritic spine density in brain-specific profilin1 mutant mice is associated with behavioral deficits

“…Whether the change in spine density in juvenile mice is causally linked to cognitive impairment and ultrasonic communication needs further investigation. Our findings strengthen the view that profilin1 is relevant for cellular processes during brain development, while profilin2 acquired specific functions in the adult brain ( Pilo Boyl et al, 2007 ; Di Domenico et al, 2021 ). It needs to be determined in future if the reported reduction in spine number in the absence of profilin1 results from impairments in spine formation, stabilization, or spine elimination.…”

Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes: a new player in neural proteome

“…All these factors are produced by neuroprogenitors during brain development. Compared to no treatment conditions, Heimdall KO cells also produced some factors that are known to be involved in neuronal brain development such as Profilin 2 [ 88 ] or Huntingtin interacting protein 1 which is known to be linked to Notch-mediated neurogenesis [ 89 ] (Supp. Data 12 ).…”

The females' response to male attractiveness: Mate choice, larvae production and differential brain protein expression

“…Several proteins involved in neurogenesis, epigenetics, and oxidative stress were differentially expressed in females after mating with attractive and less attractive males. Among these proteins, profilin (Berg, 2005; Di Domenico et al, 2021; Witke, 1998) and AF4/FMR2 family member 4 (Gu et al, 2002; Wittwer et al, 2001) are involved in neural architecture and synaptic plasticity. Histone‐lysine methyltransferase is related to memory formation (Biergans et al, 2012; Gupta et al, 2010; Li et al, 2013; Lockett et al, 2010; Miller & Sweatt, 2007) and Virilizer is responsible for mRNA m6A methylation, which is related to memory and learning (Jiang et al, 2021; Li, Yang, et al, 2019; Worpenberg et al, 2021; Yue et al, 2018), and sex differentiation (Haussmann et al, 2016; Hilfiker & Nothiger, 1991).…”

“…Several proteins involved in neurogenesis, epigenetics, and oxidative stress were differentially expressed in females after mating with attractive and less attractive males. Among these proteins, profilin (Berg, 2005;Di Domenico et al, 2021;Witke, 1998) and AF4/FMR2 family member 4 (Gu et al, 2002;Wittwer et al, 2001) are involved in neural architecture and synaptic plasticity.…”