Table 1.
Functions of formins in mammalian cells
| Formin | Localization | Cellular Function | Phenotype(s) following KO or KD |
|---|---|---|---|
| DIAPH1/DIA1(mDia1) | Phagocytic cup, cell cortex59 | Microtubule stabilization,60 phagocytosis, polarized cell migration61 | Mice devoid of mDia1 exhibit an age-dependent myelodysplastic phenotype62; lymphopenia characterized by diminished T cells in lymphoid tissues63; unilateral ventricular enlargement64 |
| DIAPH3 (mDia2) | Endosomes65 | Microtubule stabilization,66 endosome dynamics65 | Mice without mDia2 impairs cytokinesis during fetal erythropoiesis, leading to severe anemia and die in utero by embryonic day 12.567 |
| DIAPH2 (mDia3) | Kinetochore68 | Stabilized microtubules remain attached to kinetochore69 | mDia1/3 double-KO impairs tangential migration of cortical and olfactory inhibitory interneurons, mDia1/3-deficient neuroblasts exhibit reduced separation of the centrosome from the nucleus and retarded nuclear translocation70 |
| DAAM1 | Cell cortex71 | Planar cell polarity72 | DAAM1-deficient mice exhibit embryonic and neonatal lethality due to cardiac abnormalities73 |
| FMNL1 | Cell cortex, microtubule-organizing center74 | Phagocytosis75 | Depletion of FMNL1 in cytotoxic lymphocytes abrogate cell-mediated killing activity since a loss of FMNL1 reduces microtubule-organizing center polarization74 |
| FMN1 | ES, microtubules47 | ES assembly and stabilization47 | FMN1-deficient mice exhibit a reduction of digits from 5 to 4, a deformed posterior metatarsal phalangeal soft tissue fusion as well as the absence of a fibula76; formin 1 KD affects Sertoli cell actin microfilament organization, perturbing Sertoli cell tight junction barrier function, and disrupting the transport of spermatids and phagosomes in the seminiferous epithelium47 |
| INF1/FHDC1 | Microtubules77 | Microtubule stabilization77 | KD of INF1 leads to reduced level of acetylated microtubules (i.e., more stabilized and aged microtbules) and reduced microtubule bundles in multiple mammalian cells77 |
There are 15 known members of formins to date,24,25,31 however, none of these proteins have been studied in the testis functionally except a recent report on formin 1 (FMN1).47 There are 2 other earlier studies, reporting the identification of mDia1, mDia2 and mDia3 and their involvement in the acroplaxome-manchette complex in spermatids during spermiogenesis.78,79 In short, the functional significance of formins in spermatogenesis remains unknown. Thus, not all the members of formins are listed herein, selected members are listed which are likely to be involved in spermatogenesis based on their studies in other epithelia. Abbreviations used: DIAPH1/DIA1, diaphanous-related formin 1, also known as mDia1 which is the mouse version of the diaphanous homolog 1 of Drosophila; DIAPH3, diaphanous-related formin 3 or mDia2 which is also a Rho-regulated actin nucleator; DIAPH2, diaphanous-related formin 2 or mDia3; DAAM1, disheveled-associated activator of morphogenesis 1; ES, ectoplasmic specialization; FMNL1, formin-like protein 1; FMN1, formin 1; INF1/FHDC1, inverted formin1/FH2 domain containing 1, a microtubule-associated formin; KD, knock down; KO, knock out.