Morphogenesis and form · Article

Calcineurin signalling and allometric growth

Allometric growth is growth of a structure at a different rate from the rest of the body, and it changes proportions during development¹. In zebrafish fins, work by Perathoner, Daane, Harris and colleagues ties this process to a potassium channel, Kcnk5b, and to the phosphatase calcineurin, which the drug FK506 inhibits³⁵. Daane and colleagues propose that a Kcnk5b–calcineurin signalling node links bioelectric signalling to the control of organ proportion⁵.

Earliest held: 2014, Chen S, Cai D, Pearce K, Sun…
Most discussed in: Bioelectric-calcineurin signaling module…, 2018
In the library: 41 passages in 9 works
Rewritten: 2026-10-22

Allometry and the longfin mutant

Perathoner and colleagues (2014) studied the zebrafish another longfin (alf) mutant, which has proportionally enlarged fins and barbels². They reported that alf mutants carry gain-of-function mutations in kcnk5b, which encodes a two-pore domain potassium channel³. The authors presented the mutant as a way to study size regulation in vertebrates. In their account, such allometric growth explains differences between juvenile and adult forms in many organisms¹. They also link it to changes in shape and morphology during evolution¹.

Calcineurin as a general signal

Calcineurin is a widely expressed phosphatase. Perez-Neut and colleagues (2016) describe it as activated by calmodulin when intracellular calcium rises⁴. It acts on many substrates, including NFAT transcription factors, and so couples calcium to gene transcription⁴. George and Bates (2022) review calcium input to the cell cycle and name calmodulin and calcineurin as the main routes⁹. Mathews and colleagues (2022) discuss a pathway in cancer cells in which hyperpolarization, raised calcium and calcineurin lead to NFAT dephosphorylation⁸.

Kcnk5b and FK506 in the fin

Daane and colleagues (2018) noted that calcineurin inhibitors had been shown to change zebrafish fin allometry⁵. They identified kcnk5b as a key player in integrating the growth effects of calcineurin⁵. They tested whether FK506 acts by raising kcnk5b expression. Expression was not significantly altered in wild-type regenerating fins after treatment⁶. In Xenopus oocytes, FK506 lowered the conductance of wild-type Kcnk5b⁷. The authors proposed that Kcnk5b and calcineurin form a signalling node that regulates allometric growth⁵.

SourcesEach quotation was checked word for word against the passage it opens.

The growth of a structure at a different rate with respect to the rest of the body results in changes in proportions during development.Perathoner S, Daane JM, Henrion U, Seebohm G, Higdon CW…, 2014 · Bioelectric signaling regulates size in zebrafish fins · open at passage 1
The zebrafish another longfin (alf) mutant shows allometric growth resulting in proportionally enlarged fins and barbels.Perathoner S, Daane JM, Henrion U, Seebohm G, Higdon CW…, 2014 · Bioelectric signaling regulates size in zebrafish fins · open at passage 0
Here, we show that alf mutants carry gain-of-function mutations in kcnk5b, a gene encoding a two-pore domain potassium (K+) channel.Perathoner S, Daane JM, Henrion U, Seebohm G, Higdon CW…, 2014 · Bioelectric signaling regulates size in zebrafish fins · open at passage 0
CN is activated by calmodulin upon increased intracellular Ca2+ and acts on numerous substrates including transcriptor factors such as the nuclear factor of activated T cell (NFAT) proteins.Perez-Neut M, Rao VR, Gentile S, 2016 · hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer… · open at passage 5
We propose that the interaction between Kcnk5b and calcineurin acts as a signaling node to regulate allometric growth.Daane JM, Lanni J, Rothenberg I, Seebohm G, Higdon CW…, 2018 · Bioelectric-calcineurin signaling module regulates allometric growth and size… · open at passage 0
we find that expression of kcnk5b is not significantly altered in wild-type regenerating fins after FK506 treatmentDaane JM, Lanni J, Rothenberg I, Seebohm G, Higdon CW…, 2018 · Bioelectric-calcineurin signaling module regulates allometric growth and size… · open at passage 11
Oocytes expressing wild-type zebrafish Kcnk5b show decreased conductance when treated with FK506Daane JM, Lanni J, Rothenberg I, Seebohm G, Higdon CW…, 2018 · Bioelectric-calcineurin signaling module regulates allometric growth and size… · open at passage 11
This senescent phenotype is thought to occur through elevated internal calcium levels (a response to hyperpolarization), which trigger the activation of calcineurin, which in turn dephosphorylates NFATMathews J, Kuchling F, Baez-Nieto D, Diberardinis M, Pan…, 2022 · Ion Channel Drugs Suppress Cancer Phenotype in NG108-15 and U87 Cells: Toward… · open at passage 58
Calcium feeds into the cell cycle primarily by regulating calmodulin (CaM) and calcineurin (CaN)George LF, Bates EA, 2022 · Mechanisms Underlying Influence of Bioelectricity in Development · open at passage 28

Linked ideas

Ion channels and pumpspart of / contains

Kcnk5b is a two-pore domain potassium channel, and its conductance is the measured link to fin size in these studies.

Resting membrane potentialrelated to

The alf mutations raise potassium conductance and hyperpolarize cells, so voltage change is the proposed starting signal for size control.

Ion channel control of cell-cycle progression and proliferationparallels

George and Bates describe calcium acting through calmodulin and calcineurin on the cell cycle, a second setting for the same pathway.

Cancer as a bioelectric disorderrelated to

Mathews and Perez-Neut discuss calcineurin and NFAT downstream of channel drugs in cancer cells, where the effect on growth is debated.

Regenerationrelated to

Daane and colleagues tested FK506 in regenerating fins, so allometric control is studied in regrowth as well as development.

Physical forces and formrelated to

Allometry concerns how proportion and form arise from differential growth, which the fin work addresses at the level of one channel.

Kcnk5b potassium channel and calcineurin as a size rheostat in fin growthpart of / contains

Covers the calcineurin side of the same node, including how its inhibition changes fin proportion.

Where it is discussedPassages matching calcineurin, FK506, allometric growth, allometry

2018	Bioelectric-calcineurin signaling module regulates allometric growth and size… · Daane JM, Lanni J, Rothenberg I…	25
2016	hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer… · Perez-Neut M, Rao VR, Gentile S	5
2014	Bioelectric signaling regulates size in zebrafish fins · Perathoner S, Daane JM, Henrion U…	5
2015	Electron Transport Disturbances and Neurodegeneration: From Albert… · Szalárdy L, Zádori D, Klivényi P, Toldi…	1
2022	Ion Channel Drugs Suppress Cancer Phenotype in NG108-15 and U87 Cells: Toward… · Mathews J, Kuchling F, Baez-Nieto D…	1
2020	Mitochondrial Bioenergetics and Dynamics in Secretion Processes · Martínez J, Marmisolle I, Tarallo D…	1
2022	Mechanisms Underlying Influence of Bioelectricity in Development · George LF, Bates EA	1
2022	Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones · Cioffi F, Giacco A, Goglia F, Silvestri…	1
2014	Reinstatement of long-term memory following erasure of its behavioral and… · Chen S, Cai D, Pearce K, Sun PY…	1