MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes

Abstract

Polymerase I and transcript release factor (PTRF)/Cavin is a cytoplasmic protein whose expression is obligatory for caveola formation. Using biochemistry and fluorescence resonance energy transfer–based approaches, we now show that a family of related proteins, PTRF/Cavin-1, serum deprivation response (SDR)/Cavin-2, SDR-related gene product that binds to C kinase (SRBC)/Cavin-3, and muscle-restricted coiled-coil protein (MURC)/Cavin-4, forms a multiprotein complex that associates with caveolae. This complex can constitutively assemble in the cytosol and associate with caveolin at plasma membrane caveolae. Cavin-1, but not other cavins, can induce caveola formation in a heterologous system and is required for the recruitment of the cavin complex to caveolae. The tissue-restricted expression of cavins suggests that caveolae may perform tissue-specific functions regulated by the composition of the cavin complex. Cavin-4 is expressed predominantly in muscle, and its distribution is perturbed in human muscle disease associated with Caveolin-3 dysfunction, identifying Cavin-4 as a novel muscle disease candidate caveolar protein.

Impaired contractility and detrusor hypertrophy in cavin-1-deficient mice

“…Genetic ablation of cavin-1 also led to a reduced content of cavin-3 and of all caveolins. Except for the maintained level of cavin-2 in the bladder, a finding that needs to be confirmed using additional antibodies, this is largely in keeping with recent work with other cavin-1-deficient tissues (Bastiani et al, 2009;. Pacsin2 was recently shown to be associated with caveolae and to play a role in their formation (Hansen et al, 2011).…”

“…We sporadically found dead and rejected mice shortly after birth, but timed breeding needs to be undertaken to determine when the mice succumb and for what reason. The other published studies using this strain did not report increased embryonic/perinatal mortality (Bastiani et al, 2009;. If the increased mortality depends on background or breeding environment is not known.…”

“…The cavin proteins form tissue and cell-specific complexes in the cytosol. These complexes then associate with caveolins at the cytoplasmic leaflet of the plasma membrane (Bastiani et al, 2009;Briand et al, 2011;McMahon et al, 2009). It has been demonstrated that cavin-1 is critical for formation of caveolae in cultured cells , and a cavin-1 knock-out mouse model has confirmed this to be the case in some tissues also in vivo.…”

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

“…The cavin family consists of four members, cavin1 to cavin4, that are required to stabilize the Cav1 proteins and to shape caveolae (16 -19). The cavins also have the ability to bind to PtdSer (16,17,20). Furthermore, a recent study demonstrated that there are 50 cavin1 molecules per caveola (15,21).…”

Not Just Fat: The Structure and Function of the Lipid Droplet

“…Intriguingly, caveolae in adipocytes were suggested to produce TG (Ost et al 2005), which may also be transferred to LDs through the hemi-fusion channel. The functions of caveolins are closely linked to a family of cytoplasmic proteins termed cavins (Hill et al 2008;Bastiani et al 2009;Hansen et al 2009;McMahon et al 2009). PTRF/ cavin-1 is essential for the formation of caveolae (Hill et al 2008;Liu et al 2008) and, like caveolin, has been shown to be associated with LD function and lipid storage in cultured adipocytes (Aboulaich et al 2006), mice (Liu et al 2008), and human patients (Hayashi et al 2009;Rajab et al 2010).…”