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PDLIM5 is not a neuronal CaV2.2 adaptor protein

Nature Neuroscience volume 12, pages 957–958 (2009)Cite this article

To the editor:

PDLIM5 (postsynaptic density protein–95, discs-large, ZO1, Lin-11–Isl-1–Mec-3), formerly known as enigma homolog (ENH) is a ∼63-kDa cytoplasmic protein composed of a PDZ domain at the N terminus and three consecutive LIM domains at the C terminus (Supplementary Fig. 1)1. Early studies showed that protein kinase C (PKC) binds to the LIM domains1, but did not identify a role for PDLIM5 in cell function. On the basis of a combination of electrophysiological and biochemical approaches, Maeno-Hikichi et al.2 reported that PDLIM5 localizes to presynaptic terminals and developed the hypothesis that the protein interacts with CaV2.2, a presynaptic calcium channel type that is known to be sensitive to enhancement by PKC. They proposed that PDLIM5 functions as an adaptor that links PKCε to the channel, facilitating the activity of the kinase on channel kinetics and, in a second study, that this association was enhanced by Ca2+ (ref. 3). Maeno-Hikichi et al.2 suggested that regulation of the channel via this complex may be important in the modulation of synaptic strength. Since these reports, however, there has been no further analysis of this putative calcium channel modulation mechanism by other laboratories. Recent studies have suggested an association between PDLIM5 with severe psychiatric disease, such as schizophrenia and depression4,5,6. In these studies, the CaV2.2-PKCε adaptor function of PDLIM5, as suggested by Maeno-Hikichi et al.2, is generally raised as a putative pathogenic mechanism.

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Figure 1: The PDLIM5 C-terminal region, LIM1-3, did not enhance PKC-dependent facilitation of CaV2.2 current.
Figure 2: PDLIM5 and CaV2.2 do not co-immunoprecipitate from rat brain lysates.

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Authors and Affiliations

  1. Genes and Development Division, Laboratory of Synaptic Transmission, Toronto Western Research Institute, Toronto, Canada

    Sabiha R Gardezi, Alexander M Weber, Qi Li, Fiona K Wong & Elise F Stanley

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  1. Sabiha R Gardezi
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  2. Alexander M Weber
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  3. Qi Li
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Supplementary Figures 1–6, Supplementary Table 1 and Supplementary Methods (PDF 1387 kb)

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Gardezi, S., Weber, A., Li, Q. et al. PDLIM5 is not a neuronal CaV2.2 adaptor protein. Nat Neurosci 12, 957–958 (2009). https://doi.org/10.1038/nn0809-957a

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